Trial Outcomes & Findings for S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (NCT NCT03365882)

NCT ID: NCT03365882

Last Updated: 2026-02-10

Results Overview

To evaluate the efficacy of trastuzumab and pertuzumab (TP) in HER-2 amplified metastatic colorectal cancer (mCRC) by comparing progression-free survival (PFS) on TP compared to control arm of cetuximab and irinotecan (CETIRI). Progression-free survival is defined as the time from date of randomization to date of first documentation of progression. Using RECIST 1.1, progression is defined as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed and an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician, appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration (defined as, global deterioration of health status requiring discontinuation of treatment without objective evidence of progression), or death due to any cause.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 240 participants
• Primary outcome timeframe: Up to 3 years post randomization
• Results posted on: 2026-02-10

Participant Flow

240 participants were screened for HER-2 amplification, 54 participant were HER-2 positive and randomized to therapy, 1 patient is not analyzable due to withdrawal of consent and refusal of protocol treatment.

Participant milestones

Measure	Trastuzumab + Pertuzumab Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.
Randomization STARTED	26	28
Randomization Progressed and Crossed Over	0	20
Randomization COMPLETED	0	20
Randomization NOT COMPLETED	26	8
Crossover: Trastuzumab + Pertuzumab STARTED	0	20
Crossover: Trastuzumab + Pertuzumab COMPLETED	0	0
Crossover: Trastuzumab + Pertuzumab NOT COMPLETED	0	20

Reasons for withdrawal

Measure	Trastuzumab + Pertuzumab Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.
Randomization Still Receiving Protocol Treatment	2	0
Randomization Adverse Event	1	2
Randomization Refusal Unrelated to Adverse Event	0	1
Randomization Progression/Relapse	21	3
Randomization Death	1	0
Randomization Other - Not Protocol Specified	1	1
Randomization Major Protocol Deviation	0	1
Crossover: Trastuzumab + Pertuzumab Still Receiving Protocol Treatment	0	1
Crossover: Trastuzumab + Pertuzumab Progression/Relapse	0	13
Crossover: Trastuzumab + Pertuzumab Other - Not Protocol Specified	0	4
Crossover: Trastuzumab + Pertuzumab Adverse Event	0	2

Baseline Characteristics

S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Measure	Trastuzumab + Pertuzumab n=26 Participants Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=27 Participants Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.	Total n=53 Participants Total of all reporting groups
Age, Continuous	56.2 years n=4 Participants	59.1 years n=4 Participants	57.6 years n=8 Participants
Sex: Female, Male Female	13 Participants n=4 Participants	13 Participants n=4 Participants	26 Participants n=8 Participants
Sex: Female, Male Male	13 Participants n=4 Participants	14 Participants n=4 Participants	27 Participants n=8 Participants
Race/Ethnicity, Customized Hispanic · Yes	1 Participants n=4 Participants	2 Participants n=4 Participants	3 Participants n=8 Participants
Race/Ethnicity, Customized Hispanic · No	23 Participants n=4 Participants	25 Participants n=4 Participants	48 Participants n=8 Participants
Race/Ethnicity, Customized Hispanic · Unknown	2 Participants n=4 Participants	0 Participants n=4 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Race · White	19 Participants n=4 Participants	21 Participants n=4 Participants	40 Participants n=8 Participants
Race/Ethnicity, Customized Race · Black	1 Participants n=4 Participants	4 Participants n=4 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=4 Participants	1 Participants n=4 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized Race · Unknown	2 Participants n=4 Participants	1 Participants n=4 Participants	3 Participants n=8 Participants
Number of Participants with Prior Use of Irinotecan Yes	11 Participants n=4 Participants	13 Participants n=4 Participants	24 Participants n=8 Participants
Number of Participants with Prior Use of Irinotecan No	15 Participants n=4 Participants	14 Participants n=4 Participants	29 Participants n=8 Participants
HER2/CEP17 Ratio >5	19 Participants n=4 Participants	20 Participants n=4 Participants	39 Participants n=8 Participants
HER2/CEP17 Ratio <=5	7 Participants n=4 Participants	7 Participants n=4 Participants	14 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 3 years post randomization

Population: This population includes the 53 eligible and evaluable participants. 26 in the Trastuzumab + Pertuzumab arm and 27 in the Cetuximab + Irinotecan arm.

To evaluate the efficacy of trastuzumab and pertuzumab (TP) in HER-2 amplified metastatic colorectal cancer (mCRC) by comparing progression-free survival (PFS) on TP compared to control arm of cetuximab and irinotecan (CETIRI). Progression-free survival is defined as the time from date of randomization to date of first documentation of progression. Using RECIST 1.1, progression is defined as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed and an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician, appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration (defined as, global deterioration of health status requiring discontinuation of treatment without objective evidence of progression), or death due to any cause.

Outcome measures

Measure	Trastuzumab + Pertuzumab n=26 Participants Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=27 Participants Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.
Progression-free Survival(PFS)	4.7 Months Interval 1.9 to 7.6	3.7 Months Interval 1.6 to 6.7

SECONDARY outcome

Timeframe: From baseline, through duration of treatment (once per cycle while on treatment), and every 8 weeks after treatment until progression, up to 3 years after the last accrual to registration step 2

Population: This population includes the 53 eligible and evaluable participants. 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm.

To evaluate the overall response rate (ORR), including confirmed complete and partial response per RECIST 1.1, in the TP and CETIRI treatment arms. Overall response rate includes complete response(CR) and partial response(PR). Complete response is defined as complete disappearance of all target and non-target lesions and no related symptoms. Partial response is defined as a greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions for patients with at least one measurable lesion.

Outcome measures

Measure	Trastuzumab + Pertuzumab n=26 Participants Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=27 Participants Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.
Overall Response Rate (ORR) for TP and CETIRI Treatment Arms	9 Participants	7 Participants

SECONDARY outcome

Timeframe: from the date of the last accrual to registration step 2 to date of death due to any cause, up to 2 years

Population: This population includes the 53 eligible and evaluable participants. 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm.

Percentage of participants still alive 2 years after the last accrual to registration step 2. Overall survival is defined as time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.

Outcome measures

Measure	Trastuzumab + Pertuzumab n=26 Participants Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=27 Participants Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.
2 Year Overall Survival (OS) for TP and CETIRI Treatment Arms	67.1 percentage of participants Interval 44.6 to 82.1	56.7 percentage of participants Interval 35.2 to 73.5

SECONDARY outcome

Timeframe: Duration of treatment and follow-up until death or 3 years post Step 2 Randomization.

Population: Participants who were eligible and received at least one dose of protocol treatment.

Routine toxicities were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, and SAEs were evaluated according to CTCAE version 5.0. Only adverse events that are possibly, probably, or definitely related to study drug are reported.

Outcome measures

Measure	Trastuzumab + Pertuzumab n=26 Participants Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=26 Participants Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I.
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Abdominal pain	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Alanine aminotransferase increased	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Alkaline phosphatase increased	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Anemia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Anorexia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Atrial fibrillation	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Diarrhea	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Dyspnea	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Fatigue	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Gastrointestinal disorders - Other, specify	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypokalemia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypomagnesemia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Infusion related reaction	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Leukocytosis	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Lymphocyte count decreased	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Rash acneiform	0 Participants	3 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Rash maculo-papular	1 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Thromboembolic event	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Vomiting	1 Participants	1 Participants

Adverse Events

Trastuzumab + Pertuzumab

Serious events: 8 serious events

Other events: 23 other events

Deaths: 9 deaths

Cetuximab + Irinotecan

Serious events: 1 serious events

Other events: 26 other events

Deaths: 18 deaths

Crossover: Trastuz +Pertuz

Serious events: 5 serious events

Other events: 18 other events

Deaths: 12 deaths

Serious adverse events

Measure	Trastuzumab + Pertuzumab n=26 participants at risk Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=26 participants at risk Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I. The number of affected participants in All-Cause Mortality includes participants that died after they crossed over to Arm I.	Crossover: Trastuz +Pertuz n=20 participants at risk Following radiographic documentation by RECIST 1.1 of disease progression, participants initially randomized and treated with Cetuximab + Irinotecan may register to Step 3 Crossover Registration to be treated with Trastuzumab + Pertuzumab according to Arm/Group 1's description.
Cardiac disorders Atrial fibrillation	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Abdominal pain	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Diarrhea	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Nausea	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Small intestinal obstruction	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Vomiting	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Infusion related reaction	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Appendicitis	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Infections and infestations-Other	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Papulopustular rash	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Injury, poisoning and procedural complications Burn	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Aspartate aminotransferase increased	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Blood bilirubin increased	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Dehydration	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Seizure	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Skin ulceration	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Vascular disorders Hypotension	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.

Other adverse events

Measure	Trastuzumab + Pertuzumab n=26 participants at risk Participants receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Cetuximab + Irinotecan n=26 participants at risk Participants receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Participants with documented disease progression may optionally crossover to Arm I. The number of affected participants in All-Cause Mortality includes participants that died after they crossed over to Arm I.	Crossover: Trastuz +Pertuz n=20 participants at risk Following radiographic documentation by RECIST 1.1 of disease progression, participants initially randomized and treated with Cetuximab + Irinotecan may register to Step 3 Crossover Registration to be treated with Trastuzumab + Pertuzumab according to Arm/Group 1's description.
Blood and lymphatic system disorders Anemia	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	30.8% 8/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Cardiac disorders Chest pain - cardiac	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Cardiac disorders Sinus tachycardia	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Eye disorders Blurred vision	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Eye disorders Eye disorders-Other	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Abdominal distension	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Abdominal pain	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Ascites	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Bloating	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Colitis	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Constipation	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	30.8% 8/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Diarrhea	57.7% 15/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	53.8% 14/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	55.0% 11/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Dyspepsia	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Dysphagia	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Gastrointestinal disorders-Other	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Mucositis oral	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Nausea	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	50.0% 13/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	20.0% 4/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Rectal pain	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Stomach pain	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Toothache	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Gastrointestinal disorders Vomiting	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Chills	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Edema limbs	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Fatigue	34.6% 9/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	53.8% 14/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	50.0% 10/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Fever	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Flu like symptoms	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders General disorders and admin site conditions - Other	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Infusion related reaction	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Irritability	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Non-cardiac chest pain	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
General disorders Pain	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Infections and infestations-Other	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Paronychia	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Upper respiratory infection	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Infections and infestations Urinary tract infection	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Injury, poisoning and procedural complications Fracture	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Alanine aminotransferase increased	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Alkaline phosphatase increased	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Aspartate aminotransferase increased	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Blood bilirubin increased	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Creatinine increased	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Ejection fraction decreased	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Investigations-Other	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Lymphocyte count decreased	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Neutrophil count decreased	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Platelet count decreased	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations Weight loss	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Investigations White blood cell decreased	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Anorexia	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	20.0% 4/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Dehydration	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hyperglycemia	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hypoalbuminemia	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hypocalcemia	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hypokalemia	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	26.9% 7/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hypomagnesemia	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	38.5% 10/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Metabolism and nutrition disorders Hyponatremia	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Dizziness	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Back pain	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tiss disorder - Other	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Myalgia	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Dysarthria	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Dysgeusia	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Headache	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Peripheral sensory neuropathy	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Nervous system disorders Syncope	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Psychiatric disorders Anxiety	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Psychiatric disorders Depression	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Psychiatric disorders Insomnia	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Renal and urinary disorders Hematuria	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Cough	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	26.9% 7/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	26.9% 7/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	10.0% 2/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Alopecia	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Dry skin	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.4% 4/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	5.0% 1/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Pruritus	19.2% 5/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Rash acneiform	3.8% 1/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	38.5% 10/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	25.0% 5/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Rash maculo-papular	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	46.2% 12/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	35.0% 7/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Vascular disorders Hypertension	11.5% 3/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	23.1% 6/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	15.0% 3/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Vascular disorders Hypotension	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.
Vascular disorders Thromboembolic event	0.00% 0/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	7.7% 2/26 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.	0.00% 0/20 • Duration of treatment and follow up until death or 3 years post Step 2 Randomization. CTCAE version 5.0 was used for reporting SAEs and CTCAE version 4.0 was used for routine toxicity reporting. All-Cause mortality was assessed in all analyzable participants, 26 participants in the Trastuzumab + Pertuzumab arm and 27 participants in the Cetuximab + Irinotecan arm. Due to 1 participant refusal of treatment, there were only 26 participants in the Cetuximab + Irinotecan arm that were evaluable for AEs and 26 participants in the Trastuzumab + Pertuzumab arm evaluable for AEs.

Additional Information

Gastrointestinal Committee Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: scolby@fredhutch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60