Trial Outcomes & Findings for Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer (NCT NCT01412957)

Last Updated: 2017-03-15

Results Overview

Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

377 participants

Primary outcome timeframe

From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).

Results posted on

2017-03-15

Participant Flow

A total of 377 participants were randomized at 66 centers in Europe, Asia, North and South America from 8 November 2011 until 30 July 2013. Results are reported as of the primary analysis data cut-off date of 10 June 2014.

Participants were stratified according to geographic region (Europe vs Asia vs rest of the world) and Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs 2) and randomized (1:1 ratio) to 1 of 2 treatment groups.

Participant milestones

Participant milestones
Measure	Panitumumab + BSC Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone Participants received best supportive care until disease progression, withdrawal of consent, or death.
Overall Study STARTED	189	188
Overall Study COMPLETED	40	31
Overall Study NOT COMPLETED	149	157

Reasons for withdrawal

Reasons for withdrawal
Measure	Panitumumab + BSC Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone Participants received best supportive care until disease progression, withdrawal of consent, or death.
Overall Study Withdrawal by Subject	6	22
Overall Study Lost to Follow-up	7	2
Overall Study Death	136	133

Baseline Characteristics

Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panitumumab + BSC n=189 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=188 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.	Total n=377 Participants Total of all reporting groups
Age, Continuous	60.2 years STANDARD_DEVIATION 10.7 • n=93 Participants	58.7 years STANDARD_DEVIATION 11.1 • n=4 Participants	59.4 years STANDARD_DEVIATION 10.9 • n=27 Participants
Sex: Female, Male Female	82 Participants n=93 Participants	79 Participants n=4 Participants	161 Participants n=27 Participants
Sex: Female, Male Male	107 Participants n=93 Participants	109 Participants n=4 Participants	216 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	23 participants n=93 Participants	22 participants n=4 Participants	45 participants n=27 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	166 participants n=93 Participants	166 participants n=4 Participants	332 participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=93 Participants	3 participants n=4 Participants	3 participants n=27 Participants
Race/Ethnicity, Customized Asian	79 participants n=93 Participants	82 participants n=4 Participants	161 participants n=27 Participants
Race/Ethnicity, Customized White	107 participants n=93 Participants	102 participants n=4 Participants	209 participants n=27 Participants
Race/Ethnicity, Customized Other	3 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants
Geographic Region Europe	86 participants n=93 Participants	85 participants n=4 Participants	171 participants n=27 Participants
Geographic Region Asia	80 participants n=93 Participants	82 participants n=4 Participants	162 participants n=27 Participants
Geographic Region Rest of world	23 participants n=93 Participants	21 participants n=4 Participants	44 participants n=27 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0	71 participants n=93 Participants	65 participants n=4 Participants	136 participants n=27 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1	100 participants n=93 Participants	107 participants n=4 Participants	207 participants n=27 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2	18 participants n=93 Participants	16 participants n=4 Participants	34 participants n=27 Participants
Location of Primary Tumor Colon	108 participants n=93 Participants	106 participants n=4 Participants	214 participants n=27 Participants
Location of Primary Tumor Rectum	81 participants n=93 Participants	81 participants n=4 Participants	162 participants n=27 Participants
Location of Primary Tumor Missing	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants

PRIMARY outcome

Timeframe: From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).

Population: Intent to Treat (ITT) Analysis Set (all randomized participants); participants in the ITT Analysis Set were required to have wild-type KRAS exon 2 (codons 12 and 13, alleles G12A, G12D, G12R, G12C, G12S, G12V, or G13D) per protocol.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=189 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=188 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Overall Survival	10.0 months Interval 8.7 to 11.4	7.4 months Interval 5.8 to 9.3

SECONDARY outcome

Population: ITT Analysis Set

Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death. Progressive disease (PD): At least a 20% increase in the size of target lesions compared with the smallest size since treatment started and an absolute increase of at least 5 mm, any new lesions or an increase in size of non-target lesions thought be ≥ 20% and an absolute increase of at least 5 mm, or significant increase in pleural effusions, ascites or other fluid collections with cytologic proof of malignancy. Participants who were alive and did not meet the criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=189 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=188 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Progression-free Survival	3.6 months Interval 3.4 to 5.3	1.7 months Interval 1.6 to 1.9

SECONDARY outcome

Timeframe: From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).

Population: Wild-type RAS Efficacy Analysis Set (subset of participants in the ITT Analysis Set without mutation in exon 2, 3, and 4 of KRAS or NRAS)

A secondary efficacy endpoint was overall survival in participants with wild-type rat sarcoma viral oncogene homolog (RAS) (without mutation in exons 2 \[codons 12 and 13\], 3 \[codons 59 and 61\], and 4 \[codons 117 and 146\] of KRAS and neuroblastoma RAS viral oncogene (NRAS)). In participants with wild-type RAS, RAS mutation status was defined by KRAS exon 2 mutation status per clinical trial assay testing and mutation status of KRAS exon 3 and 4 and NRAS exons 2, 3 and 4 per Sanger bi-directional sequencing. Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=142 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=128 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Overall Survival in Participants With Wild-type RAS	10.0 months Interval 8.7 to 11.6	6.9 months Interval 5.2 to 7.9

SECONDARY outcome

Population: Wild-type RAS Efficacy Analysis Set

PFS was defined as the time from the randomization date to the date of disease progression per RECIST version 1.1 or death. Progressive disease (PD): At least a 20% increase in the size of target lesions compared with the smallest size since treatment started and an absolute increase of at least 5 mm, any new lesions, or an increase in size of non-target lesions thought be ≥ 20% with an absolute increase of at least 5 mm, or significant increase in pleural effusions, ascites or other fluid collections with cytologic proof of malignancy. Participants who were alive and did not meet the criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=142 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=128 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Progression Free Survival (PFS) in Participants With Wild-type RAS	5.2 months Interval 3.5 to 5.3	1.7 months Interval 1.6 to 2.2

SECONDARY outcome

Timeframe: Response was assessed at Week 4, Week 8, and then every 8 weeks until the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).

Population: ITT analysis set

Objective response rate (ORR) is defined as the percentage of participants with either a complete response (CR) or partial response (PR) per RECIST version 1.1. Radiographic tumor assessments and investigator's assessment of response were performed at Week 4, Week 8, and then every 8 weeks until disease progression (radiographic or clinical progression). CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesions not qualifying for either CR or PD and no new lesions.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=189 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=188 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Objective Response Rate	26.98 percentage of participants Interval 20.8 to 33.91	1.60 percentage of participants Interval 0.33 to 4.59

SECONDARY outcome

Timeframe: Response was assessed at Week 4, Week 8, and then every 8 weeks until the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).

Population: Wild-type RAS Efficacy Analysis Set

Objective response rate is defined as the percentage of participants with either a complete response (CR) or partial response (PR) per RECIST version 1.1. Radiographic tumor assessments and investigator's assessment of response were performed at Week 4, Week 8, and then every 8 weeks until disease progression (radiographic or clinical progression). CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesions not qualifying for either CR or PD and no new lesions.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=142 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=128 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Objective Response Rate in Participants With Wild-type RAS	30.99 percentage of participants Interval 23.5 to 39.28	2.34 percentage of participants Interval 0.49 to 6.7

SECONDARY outcome

Timeframe: From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively.

Population: Safety Analysis Set (all randomized participants)

The severity of each AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Grade 1 = Mild; 2 = Moderate (discomfort enough to cause interference with usual activity); 3 = Severe (incapacitating with inability to work or do usual activity); 4 = Life-threatening and 5 = Fatal), with the exception of the skin-or nail-related AEs which were graded using a CTCAE version 3.0 with modifications. A serious AE was defined as an AE that met at least 1 of the following criteria: • fatal, • life-threatening, • required in-patient hospitalization or prolongation of existing hospitalization, • resulted in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other medically important serious event. Treatment-related AEs (TRAEs) are those the investigator considered there was reasonable possibility that the event might have been caused by study drug.

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=189 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone n=188 Participants Participants received best supportive care until disease progression, withdrawal of consent, or death.
Number of Participants With Adverse Events (AEs) Treatment-related AE with worst grade of 3	41 participants	1 participants
Number of Participants With Adverse Events (AEs) Treatment-related AE with worst grade of 4	4 participants	1 participants
Number of Participants With Adverse Events (AEs) Treatment-related AE with worst grade of 5	0 participants	1 participants
Number of Participants With Adverse Events (AEs) Serious treatment-related AE	2 participants	3 participants
Number of Participants With Adverse Events (AEs) TRAE leading to discontinuation of panitumumab	1 participants	NA participants Not applicable for BSC Alone arm
Number of Participants With Adverse Events (AEs) Any adverse event (AE)	184 participants	115 participants
Number of Participants With Adverse Events (AEs) AE with worst grade of 3	70 participants	29 participants
Number of Participants With Adverse Events (AEs) AE with worst grade of 4	17 participants	5 participants
Number of Participants With Adverse Events (AEs) AE with worst grade of 5	8 participants	15 participants
Number of Participants With Adverse Events (AEs) Serious adverse event (SAE)	48 participants	37 participants
Number of Participants With Adverse Events (AEs) AE leading to discontinuation of panitumumab	20 participants	NA participants Not applicable for BSC Alone arm
Number of Participants With Adverse Events (AEs) Treatment-related adverse event (TRAE)	166 participants	7 participants

SECONDARY outcome

Timeframe: Baseline (pre-dose), Week 1 and Week 7 (post-dose) and 4 weeks after the last dose (Safety Follow-up visit)

Population: QTc Analysis Set is defined as the subset of participants in the Safety Analysis Set who received at least one panitumumab dose and were enrolled at the limited number of sites participating in QTc evaluation and had baseline and at least 1 post-baseline QTc assessment.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by electrocardiogram (ECG). QTc is the QT interval corrected for heart rate. To evaluate the effect of panitumumab treatment on the QTc interval length among participants treated with panitumumab, ECGs were collected at the following time points from participants randomized to panitumumab arm at a limited number of sites: Week 1 prior to the first panitumumab infusion (Baseline) and within 30 minutes following the end of the first infusion of panitumumab (Cmax), Week 7 after 3 doses of panitumumab (steady state), and at the safety follow-up visit. The ECGs were submitted for independent central review to calculate the reported QTc interval. QTc was calculated using both the Bazett correction (QTcB) and the Fridericia correction (QTcF).

Outcome measures

Outcome measures
Measure	Panitumumab + BSC n=53 Participants Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.	BSC Alone Participants received best supportive care until disease progression, withdrawal of consent, or death.
Maximum Post-baseline Change From Baseline in Corrected QT (QTc) Interval QTcF	14.58 msec Standard Deviation 13.60	—
Maximum Post-baseline Change From Baseline in Corrected QT (QTc) Interval QTcB	12.57 msec Standard Deviation 12.15	—

Adverse Events

Panitumumab Plus BSC

Serious events: 48 serious events

Other events: 174 other events

Deaths: 0 deaths

BSC Alone

Serious events: 37 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Panitumumab Plus BSC n=189 participants at risk	BSC Alone n=188 participants at risk Participants received best supportive care until disease progression, withdrawal of consent, or death.
Blood and lymphatic system disorders Anaemia	7.9% 15/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.5% 16/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	14.8% 28/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.6% 18/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	7.9% 15/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.4% 12/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	13.2% 25/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.7% 7/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dyspepsia	5.3% 10/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.1% 2/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	5.8% 11/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.3% 10/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Stomatitis	6.3% 12/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	6.3% 12/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.7% 7/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	14.8% 28/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.4% 14/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	8.5% 16/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 9/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Conjunctivitis	6.3% 12/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Paronychia	14.3% 27/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight decreased	6.9% 13/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 4/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Decreased appetite	9.5% 18/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.5% 16/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	6.9% 13/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypokalaemia	5.3% 10/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypomagnesaemia	28.0% 53/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.1% 2/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	6.3% 12/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.3% 10/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Acne	13.8% 26/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dermatitis acneiform	28.6% 54/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dry skin	15.3% 29/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.53% 1/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Erythema	12.2% 23/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	10.1% 19/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Pruritus	24.9% 47/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash	38.6% 73/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.1% 2/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.3% 10/189 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/188 • From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.