Trial Outcomes & Findings for Cabazitaxel Compared to Topotecan for the Treatment of Small Cell Lung Cancer (NCT NCT01500720)

Last Updated: 2015-04-13

Results Overview

PFS was defined as the time interval from the date of randomization to the date of occurrence of the first documented tumor progression or death due to any cause, whichever came first. Median PFS was estimated using the Kaplan-Meier method. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

179 participants

Primary outcome timeframe

Randomization to first tumor progression/clinical deterioration or death (maximum 7.6 months)

Results posted on

2015-04-13

Participant Flow

A total of 232 participants were screened of which 53 were screen failure and 179 were randomized.

Participant milestones

Participant milestones
Measure	Cabazitaxel Cabazitaxel (XRP6258) 25 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Overall Study STARTED	90	89
Overall Study Treated	89	88
Overall Study COMPLETED	85	80
Overall Study NOT COMPLETED	5	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Cabazitaxel Cabazitaxel (XRP6258) 25 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Overall Study Randomized But Not Treated	1	1
Overall Study Other	4	8

Baseline Characteristics

Cabazitaxel Compared to Topotecan for the Treatment of Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabazitaxel n=90 Participants Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=89 Participants Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Total n=179 Participants Total of all reporting groups
Age, Continuous	59.9 years STANDARD_DEVIATION 9.4 • n=5 Participants	61.6 years STANDARD_DEVIATION 10.0 • n=7 Participants	60.7 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	62 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized Race: Caucasian/White	80 participants n=5 Participants	82 participants n=7 Participants	162 participants n=5 Participants
Race/Ethnicity, Customized Race: Black	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Race: Asian/Oriental	9 participants n=5 Participants	4 participants n=7 Participants	13 participants n=5 Participants
Race/Ethnicity, Customized Race: Other	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Hispanic	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Not Hispanic	86 participants n=5 Participants	86 participants n=7 Participants	172 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	31 participants n=5 Participants	17 participants n=7 Participants	48 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	59 participants n=5 Participants	71 participants n=7 Participants	130 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Primary Tumor Site Lungs	16 participants n=5 Participants	20 participants n=7 Participants	36 participants n=5 Participants
Primary Tumor Site Right Lung	33 participants n=5 Participants	43 participants n=7 Participants	76 participants n=5 Participants
Primary Tumor Site Left Lung	40 participants n=5 Participants	26 participants n=7 Participants	66 participants n=5 Participants
Primary Tumor Site Other: Mediastino-Hilar	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Stage at Diagnosis IIA	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Stage at Diagnosis IIB	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Stage at Diagnosis IIIA	2 participants n=5 Participants	12 participants n=7 Participants	14 participants n=5 Participants
Stage at Diagnosis IIIB	25 participants n=5 Participants	15 participants n=7 Participants	40 participants n=5 Participants
Stage at Diagnosis IV	57 participants n=5 Participants	55 participants n=7 Participants	112 participants n=5 Participants
Stage at Diagnosis Unknown	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Number of Organs Involved	3.6 organs STANDARD_DEVIATION 1.3 • n=5 Participants	3.8 organs STANDARD_DEVIATION 1.4 • n=7 Participants	3.7 organs STANDARD_DEVIATION 1.3 • n=5 Participants

PRIMARY outcome

Timeframe: Randomization to first tumor progression/clinical deterioration or death (maximum 7.6 months)

Population: Intent-to-treat (ITT) population included all randomized participants.

Outcome measures

Outcome measures
Measure	Cabazitaxel n=90 Participants Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=89 Participants Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Progression Free Survival (PFS)	1.4 months Interval 1.4 to 1.5	3.0 months Interval 2.7 to 4.1

SECONDARY outcome

Timeframe: From randomization to date of death (maximum 15 months)

Population: ITT population.

Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the last date the participant was known to be alive. Median time was estimated by Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Cabazitaxel n=90 Participants Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=89 Participants Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Overall Survival	5.2 months Interval 3.38 to 6.11	6.8 months Interval 5.03 to 8.08

SECONDARY outcome

Timeframe: Week 12

Population: ITT population.

Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Death due to disease progression within 12 weeks without radiological documentation of progressive disease was counted as an event. Percentage of participants who were progression free at week 12 are reported.

Outcome measures

Outcome measures
Measure	Cabazitaxel n=90 Participants Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=89 Participants Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Progression Free Rate at Week 12	18.9 percentage of participants Interval 11.4 to 28.5	52.8 percentage of participants Interval 41.9 to 63.5

SECONDARY outcome

Timeframe: Randomization to disease progression/occurrence (maximum 7.6 months)

Population: ITT population.

Overall objective tumor response was defined as the proportion of participants with confirmed RECIST 1.1 achieving a complete response (CR) or partial response (PR). CR was defined as disappearance of all target/non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants with overall objective tumor response is reported.

Outcome measures

Outcome measures
Measure	Cabazitaxel n=90 Participants Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=89 Participants Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Overall Objective Tumor Response Rate	0 percentage of participants Interval 0.0 to 4.9	10.1 percentage of participants Interval 4.5 to 19.0

Adverse Events

Cabazitaxel

Serious events: 36 serious events

Other events: 67 other events

Deaths: 0 deaths

Topotecan

Serious events: 41 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

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	Cabazitaxel n=89 participants at risk Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=88 participants at risk Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Infections and infestations Neutropenic infection	4.5% 4/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	5.7% 5/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Neutropenic sepsis	3.4% 3/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Bronchitis	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Clostridium difficile colitis	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Lung infection	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Pneumonia	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Postoperative wound infection	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Infections and infestations Respiratory tract infection	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Febrile neutropenia	6.7% 6/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	11.4% 10/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Neutropenia	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	2.3% 2/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Anaemia	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Leukopenia	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Lymph node pain	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Thrombocytopenia	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	11.4% 10/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Pancytopenia	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	2.3% 2/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Metabolism and nutrition disorders Hyponatraemia	3.4% 3/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Metabolism and nutrition disorders Hypokalaemia	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Metabolism and nutrition disorders Dehydration	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Nervous system disorders Convulsion	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Nervous system disorders Epilepsy	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Nervous system disorders Paraparesis	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Nervous system disorders Sciatica	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Cardiac disorders Pericardial effusion	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Cardiac disorders Cardiopulmonary failure	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	2.3% 2/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Vascular disorders Hypotension	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	2.3% 2/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Pulmonary microemboli	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	1.1% 1/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Abdominal pain	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Anal haemorrhage	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Diarrhoea	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Gastrointestinal pain	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).

Other adverse events
Measure	Cabazitaxel n=89 participants at risk Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.	Topotecan n=88 participants at risk Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Blood and lymphatic system disorders Anaemia	4.5% 4/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	20.5% 18/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Febrile neutropenia	4.5% 4/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Leukopenia	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Neutropenia	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	22.7% 20/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	15.9% 14/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Metabolism and nutrition disorders Decreased appetite	18.0% 16/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	14.8% 13/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Nervous system disorders Dizziness	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	5.7% 5/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Nervous system disorders Headache	6.7% 6/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	10.2% 9/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Cough	11.2% 10/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	9.1% 8/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.1% 9/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	23.9% 21/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Abdominal pain	10.1% 9/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	3.4% 3/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Abdominal pain upper	5.6% 5/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	2.3% 2/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Constipation	9.0% 8/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	10.2% 9/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Diarrhoea	20.2% 18/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	10.2% 9/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Nausea	15.7% 14/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	12.5% 11/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Stomatitis	9.0% 8/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	3.4% 3/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Gastrointestinal disorders Vomiting	16.9% 15/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	8.0% 7/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Skin and subcutaneous tissue disorders Alopecia	5.6% 5/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	5.7% 5/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 2/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Musculoskeletal and connective tissue disorders Back pain	9.0% 8/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	5.7% 5/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.1% 9/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	5.7% 5/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Musculoskeletal and connective tissue disorders Myalgia	5.6% 5/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	0.00% 0/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
General disorders Asthenia	11.2% 10/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	19.3% 17/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
General disorders Fatigue	29.2% 26/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	25.0% 22/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
General disorders Non-cardiac chest pain	6.7% 6/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
General disorders Oedema peripheral	1.1% 1/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	5.7% 5/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
General disorders Pyrexia	4.5% 4/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	8.0% 7/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Investigations Neutrophil count decreased	3.4% 3/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	6.8% 6/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).
Investigations Weight decreased	7.9% 7/89 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).	4.5% 4/88 • All Adverse Events (AE) were collected from signature of the informed consent form until 30 days after last study treatment administration (maximum 66 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study treatment administration until 30 days after the last dose of study treatment). Safety population all randomized participants who received at least one dose of study medication (treated).