Trial Outcomes & Findings for An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer (NCT NCT00410761)

Last Updated: 2025-09-24

Results Overview

Median time to progression (months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Values here are estimated (from a Weibull model) as the medians were not met.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

331 participants

Primary outcome timeframe

RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent.

Results posted on

2025-09-24

Participant Flow

A total of 331 participants were enrolled in the study. The study was conducted at 60 study sites in 23 countries. First participant enrolled 23 November 2006, last participant enrolled 19 October 2007.

Participant milestones

Participant milestones
Measure	Vandetanib 300 mg/Vandetanib 300 mg Participants received vandetanib 300 mg orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period. Upon disease progression or implementation of protocol amendment 6, participants who were unblinded were given the option to enter the open-label treatment period and continue to receive vandetanib 300 mg orally once daily for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.	Placebo/Vandetanib 300 mg Participants received placebo matched to vandetanib orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period. Upon disease progression or implementation of protocol amendment 6, participants who were unblinded were given the option to enter the open-label treatment period and receive vandetanib 300 mg orally once daily for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.
Randomized Treatment Period STARTED	231	100
Randomized Treatment Period Received Randomized Treatment	231	99
Randomized Treatment Period COMPLETED	14	1
Randomized Treatment Period NOT COMPLETED	217	99
Open-Label Treatment Period STARTED	109	79
Open-Label Treatment Period COMPLETED	28	21
Open-Label Treatment Period NOT COMPLETED	81	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Vandetanib 300 mg/Vandetanib 300 mg Participants received vandetanib 300 mg orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period. Upon disease progression or implementation of protocol amendment 6, participants who were unblinded were given the option to enter the open-label treatment period and continue to receive vandetanib 300 mg orally once daily for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.	Placebo/Vandetanib 300 mg Participants received placebo matched to vandetanib orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period. Upon disease progression or implementation of protocol amendment 6, participants who were unblinded were given the option to enter the open-label treatment period and receive vandetanib 300 mg orally once daily for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.
Randomized Treatment Period Adverse Event	34	3
Randomized Treatment Period Objective Disease Progression	103	68
Randomized Treatment Period Withdrawal by Subject	11	6
Randomized Treatment Period Other	69	21
Randomized Treatment Period Randomized but did not Receive Treatment	0	1
Open-Label Treatment Period Adverse Event	13	15
Open-Label Treatment Period Objective Disease Progression	42	27
Open-Label Treatment Period Withdrawal by Subject	8	7
Open-Label Treatment Period Other	18	9

Baseline Characteristics

An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily	Total n=331 Participants Total of all reporting groups
Age, Continuous	50.7 years n=5 Participants	53.4 years n=7 Participants	52 years n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	44 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	56 Participants n=7 Participants	190 Participants n=5 Participants

PRIMARY outcome

Timeframe: RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent.

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Progression-Free Survival(PFS)	30.5 Months PFS is a time to event endpoint and because the medians were not met in this study there is no appropriate measure of dispersion of the median	19.2 Months PFS is a time to event endpoint and because the medians were not met in this study there is no appropriate measure of dispersion of the median

SECONDARY outcome

Timeframe: RECIST assessments performed at screening (within 3 weeks before randomisation), then every 12 weeks. For patients with objective response of CR or PR, an additional confirmatory scan was performed ≥4 weeks following the date of first response.

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)\>= 12 weeks, progressive disease (PD) or NE.

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Objective Response Rate (ORR)	104 Participants	13 Participants

SECONDARY outcome

Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) \>= 12 weeks

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Disease Control Rate (DCR)	200 Participants	71 Participants

SECONDARY outcome

Population: DoR is a time to event endpoint and because the medians were not met in this study there is no appropriate measure of dispersion of the median

Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment). Values are estimated as the medians weren't met

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=104 Participants Vandetanib (300 mg daily)	Placebo n=13 Participants Placebo daily
Duration of Response (DoR)	22.2 Months DoR is a time to event endpoint and because the medians were not met in this study there is no appropriate measure of dispersion of the median	16.3 Months DoR is a time to event endpoint and because the medians were not met in this study there is no appropriate measure of dispersion of the median

SECONDARY outcome

Timeframe: From date of randomization until death, up to approximately 105 months

OS is defined as the time from the date of randomization until death.

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Overall Survival (OS)	81.6 Months Interval 64.6 to 98.5	80.4 Months Interval 52.5 to NA indicates that the upper limit of confidence interval was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Blood samples for analysis of CTN were taken at screening baseline (average of 0, 1, 4 and 8 hours), then every 4 weeks until discontinuation and 60 day follow up

Best biochemical response was calculated from assessments at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for PR or CR were first met. CR and PR being defined according to level of CTN.

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Biochemical Response Calcitonin (CTN)	160 Participants	3 Participants

SECONDARY outcome

Timeframe: Blood samples for analysis of CEA were taken at screening baseline (average of 0, 1, 4 and 8 hours), then every 4 weeks until discontinuation and 60 day follow up

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Biochemical Response Carcinoembryonic Antigen (CEA)	119 Participants	2 Participants

SECONDARY outcome

Timeframe: During the last week of the screening period (Day -7 to Day 0), the brief pain inventory (BPI) and opioid analgesic use were self-reported once a day for 4 days to establish baseline, then every week during blinded study treatment, up to discontinuation.

TWP was derived using the worst pain score from brief pain inventory (BPI) and patient reported opioid analgesic use. BPI uses 0 to 10 numeric rating scales asking subjects to rate their pain. TWP results are presented.

Outcome measures

Outcome measures
Measure	Vandetanib 300 mg n=231 Participants Vandetanib (300 mg daily)	Placebo n=100 Participants Placebo daily
Time to Worsening of Pain (TWP)	7.85 Months Interval 5.39 to 12.16	3.25 Months Interval 1.87 to 5.26

Adverse Events

Randomized Treatment Period: Vandetanib 300 mg

Serious events: 92 serious events

Other events: 226 other events

Deaths: 66 deaths

Randomized Treatment Period: Placebo

Serious events: 16 serious events

Other events: 87 other events

Deaths: 10 deaths

Open-Label Treatment Period: Vandetanib 300 mg/Vandetanib 300 mg

Serious events: 53 serious events

Other events: 32 other events

Deaths: 52 deaths

Open-Label Treatment Period: Placebo/Vandetanib 300 mg

Serious events: 36 serious events

Other events: 70 other events

Deaths: 41 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Randomized Treatment Period: Vandetanib 300 mg n=231 participants at risk Participants received vandetanib 300 mg orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period.	Randomized Treatment Period: Placebo n=99 participants at risk Participants received placebo matched to vandetanib orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period.	Open-Label Treatment Period: Vandetanib 300 mg/Vandetanib 300 mg n=109 participants at risk Participants who received vandetanib 300 mg during the blinded randomized treatment period and who were unblinded due to disease progression or as a result of protocol amendment 6 were given the option to continue to receive vandetanib 300 mg orally once daily in the open-label treatment period for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.	Open-Label Treatment Period: Placebo/Vandetanib 300 mg n=79 participants at risk Participants who received placebo matched to vandetanib during the blinded randomized treatment period and who were unblinded due to disease progression or as a result of protocol amendment 6 were given the option to receive vandetanib 300 mg orally once daily in the open-label treatment period for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.
Blood and lymphatic system disorders Anaemia	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Blood and lymphatic system disorders Disseminated Intravascular Coagulation	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Blood and lymphatic system disorders Thrombocytopenia	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.7% 4/109 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Arrhythmia	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Atrial Fibrillation	0.87% 2/231 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Bradycardia	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Cardiac Failure Acute	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Cardio-Respiratory Arrest	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Cardiovascular Insufficiency	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Myocardial Infarction	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Pericardial Effusion	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Pericardial Haemorrhage	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Pericarditis	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Cardiac disorders Stress Cardiomyopathy	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Congenital, familial and genetic disorders Patent Ductus Arteriosus	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Endocrine disorders Cushing's Syndrome	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Cataract	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Glaucoma	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Retinal Artery Occlusion	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Retinal Detachment	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Vision Blurred	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Abdominal Pain	1.7% 4/231 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Colitis	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Diarrhoea	2.6% 6/231 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.5% 2/79 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Dry Mouth	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Dysphagia	0.87% 2/231 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Faecaloma	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Gastritis	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Gastrointestinal Inflammation	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Ileus	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Mechanical Ileus	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Nausea	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Obstructive Pancreatitis	0.00% 0/231 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Pancreatitis	0.43% 1/231 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.

Other adverse events
Measure	Randomized Treatment Period: Vandetanib 300 mg n=231 participants at risk Participants received vandetanib 300 mg orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period.	Randomized Treatment Period: Placebo n=99 participants at risk Participants received placebo matched to vandetanib orally once daily until objective disease progression, any other withdrawal criteria was met or at the investigator's discretion, the approval and implementation of protocol amendment 6 during the blinded randomized treatment period.	Open-Label Treatment Period: Vandetanib 300 mg/Vandetanib 300 mg n=109 participants at risk Participants who received vandetanib 300 mg during the blinded randomized treatment period and who were unblinded due to disease progression or as a result of protocol amendment 6 were given the option to continue to receive vandetanib 300 mg orally once daily in the open-label treatment period for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.	Open-Label Treatment Period: Placebo/Vandetanib 300 mg n=79 participants at risk Participants who received placebo matched to vandetanib during the blinded randomized treatment period and who were unblinded due to disease progression or as a result of protocol amendment 6 were given the option to receive vandetanib 300 mg orally once daily in the open-label treatment period for as long as they still benefitted of it per investigator judgement or until they were given another anti-cancer therapy.
Ear and labyrinth disorders Vertigo	4.3% 10/231 • Number of events 12 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.0% 2/99 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Endocrine disorders Hypothyroidism	6.9% 16/231 • Number of events 19 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Corneal Opacity	4.8% 11/231 • Number of events 11 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Eye disorders Vision Blurred	8.2% 19/231 • Number of events 23 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Abdominal Pain	14.3% 33/231 • Number of events 50 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 5/99 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Abdominal Pain Upper	10.0% 23/231 • Number of events 33 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	7.1% 7/99 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Constipation	6.1% 14/231 • Number of events 21 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 5/99 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	11.4% 9/79 • Number of events 9 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Diarrhoea	53.2% 123/231 • Number of events 180 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	27.3% 27/99 • Number of events 36 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.7% 4/109 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	40.5% 32/79 • Number of events 39 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Dry Mouth	9.5% 22/231 • Number of events 22 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	8.9% 7/79 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Dyspepsia	12.1% 28/231 • Number of events 33 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	4.0% 4/99 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Nausea	32.0% 74/231 • Number of events 97 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	16.2% 16/99 • Number of events 16 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	4.6% 5/109 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	22.8% 18/79 • Number of events 24 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Toothache	3.0% 7/231 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 5/99 • Number of events 17 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Gastrointestinal disorders Vomiting	14.3% 33/231 • Number of events 45 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	7.1% 7/99 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	11.4% 9/79 • Number of events 9 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
General disorders Asthenia	14.7% 34/231 • Number of events 39 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	12.1% 12/99 • Number of events 12 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	15.2% 12/79 • Number of events 13 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
General disorders Fatigue	23.4% 54/231 • Number of events 64 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	23.2% 23/99 • Number of events 27 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	16.5% 13/79 • Number of events 16 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
General disorders Pyrexia	7.8% 18/231 • Number of events 20 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/79 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Infections and infestations Bronchitis	4.8% 11/231 • Number of events 11 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.1% 6/99 • Number of events 8 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.5% 2/79 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Infections and infestations Folliculitis	3.5% 8/231 • Number of events 9 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Infections and infestations Influenza	6.9% 16/231 • Number of events 16 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.8% 3/79 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Infections and infestations Nasopharyngitis	12.6% 29/231 • Number of events 43 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	9.1% 9/99 • Number of events 12 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Infections and infestations Upper Respiratory Tract Infection	8.2% 19/231 • Number of events 27 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	10.1% 8/79 • Number of events 13 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Infections and infestations Urinary Tract Infection	6.9% 16/231 • Number of events 27 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.1% 6/99 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Investigations Electrocardiogram Qt Prolonged	13.9% 32/231 • Number of events 46 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	8.9% 7/79 • Number of events 8 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Investigations Weight Decreased	11.7% 27/231 • Number of events 28 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	10.1% 10/99 • Number of events 10 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Investigations Weight Increased	2.6% 6/231 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/99 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Metabolism and nutrition disorders Decreased Appetite	18.2% 42/231 • Number of events 53 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	13.1% 13/99 • Number of events 13 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	21.5% 17/79 • Number of events 19 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Metabolism and nutrition disorders Hypocalcaemia	9.5% 22/231 • Number of events 27 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	8.9% 7/79 • Number of events 9 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Arthralgia	8.2% 19/231 • Number of events 24 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	10.1% 10/99 • Number of events 13 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Back Pain	10.0% 23/231 • Number of events 37 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	20.2% 20/99 • Number of events 41 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.5% 6/109 • Number of events 9 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.8% 3/79 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Bone Pain	4.3% 10/231 • Number of events 10 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 5/99 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Muscle Spasms	6.1% 14/231 • Number of events 16 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.0% 1/99 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	7.8% 18/231 • Number of events 24 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.1% 6/99 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.5% 2/79 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	5.2% 12/231 • Number of events 20 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	10.1% 10/99 • Number of events 14 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	7.6% 6/79 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Myalgia	4.3% 10/231 • Number of events 11 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.0% 2/99 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 2 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Neck Pain	7.4% 17/231 • Number of events 20 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	9.1% 9/99 • Number of events 10 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.3% 1/79 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Pain In Extremity	7.4% 17/231 • Number of events 24 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	14.1% 14/99 • Number of events 17 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	2.8% 3/109 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	7.6% 6/79 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Nervous system disorders Dizziness	9.1% 21/231 • Number of events 24 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 5/99 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.92% 1/109 • Number of events 1 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	8.9% 7/79 • Number of events 7 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Nervous system disorders Dysgeusia	8.7% 20/231 • Number of events 22 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	0.00% 0/109 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.8% 3/79 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Nervous system disorders Headache	26.8% 62/231 • Number of events 138 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	9.1% 9/99 • Number of events 13 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.7% 4/109 • Number of events 6 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	6.3% 5/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.
Nervous system disorders Paraesthesia	5.6% 13/231 • Number of events 15 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	3.0% 3/99 • Number of events 3 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	1.8% 2/109 • Number of events 4 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.	5.1% 4/79 • Number of events 5 • Serious adverse events(SAEs) and all-cause mortality(deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 212 months. Other (non-serious) AEs were reported from randomization (Day 1) up to data cut-off date 01-Jun-2010, approximately 42 months. AEs and SAEs were collected from Day 1 to cut-off date 01-Jun-2010 and were presented in clinical database. After this cut-off date, SAEs were reported in pharmacovigilance database, but no non-serious AEs were reported. The safety population included all participants who received at least 1 dose of vandetanib/placebo. All-cause mortality (deaths) was assessed in all randomized participants.