Trial Outcomes & Findings for A Study of Aflibercept Versus Placebo With FOLFIRI in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin Chemotherapy (NCT NCT01661270)

Last Updated: 2016-10-18

Results Overview

PFS was defined as the time interval from the date of randomization to the date of first observation of either tumor progression or death due to any cause. Tumor assessment was performed by Independent Review Committee (IRC) as per response evaluation criteria in solid tumors (RECIST) version 1.0. Progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase and at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was calculated by Kaplan-Meier estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

332 participants

Primary outcome timeframe

26.7 months

Results posted on

2016-10-18

Participant Flow

The study was conducted at 37 centers in 5 countries. A total of 332 participants were randomized between 17 July 2012 and 18 March 2014.

Due to treatment kit misallocation, part of the patients randomized to placebo received aflibercept for 1/several treatment cycles and are presented as a separate group for safety evaluation. EOT criteria were: disease progression/death, un-tolerable toxicity, consent withdrawal/Investigator decision.

Participant milestones

Participant milestones
Measure	Placebo Placebo for aflibercept intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.
Overall Study STARTED	109	223
Overall Study Adverse Event	26	47
Overall Study Disease Progression	67	118
Overall Study Physician Decision	1	8
Overall Study Participant's Request	15	48
Overall Study Other Reasons	0	2
Overall Study COMPLETED	109	223
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Aflibercept Versus Placebo With FOLFIRI in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=109 Participants Placebo for IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept n=223 Participants Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Total n=332 Participants Total of all reporting groups
Age, Continuous	53.0 years STANDARD_DEVIATION 11.3 • n=5 Participants	55.1 years STANDARD_DEVIATION 10.9 • n=7 Participants	54.4 years STANDARD_DEVIATION 11.0 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	95 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	128 Participants n=7 Participants	191 Participants n=5 Participants

PRIMARY outcome

Timeframe: 26.7 months

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

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants Placebo for IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept n=223 Participants Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.
Progression-free Survival (PFS)	5.59 months Interval 4.632 to 6.111	6.93 months Interval 6.045 to 7.655

SECONDARY outcome

Timeframe: 31.6 months

Population: ITT population.

OS was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the earliest between the last date of the participants was known to be alive and the study cut-off date. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants Placebo for IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept n=233 Participants Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.
Overall Survival (OS)	11.93 months Interval 10.086 to 14.292	14.59 months Interval 13.175 to 16.46

SECONDARY outcome

Timeframe: 26.6 months

Population: ITT population.

Objective response rate was defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR), as assessed by Investigators and the IRC according to RECIST 1.0 criteria, relative to the total number of participants in the relevant analysis population. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions.

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants Placebo for IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept n=233 Participants Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.
Percentage of Participants With Objective Response	3.7 percentage of participants Insufficient number of participants for the CI to be calculated	18.4 percentage of participants Interval 13.3 to 23.5

Adverse Events

Placebo Only

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

Aflibercept Only

Serious events: 30 serious events

Other events: 109 other events

Deaths: 0 deaths

Mixed Administration (Placebo and Aflibercept)

Serious events: 43 serious events

Other events: 188 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Serious adverse events
Measure	Placebo Only n=33 participants at risk Placebo for IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept Only n=111 participants at risk Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Mixed Administration (Placebo and Aflibercept) n=188 participants at risk Participants who were originally randomized to receive either Placebo or Aflibercept, actually received both the treatment (Placebo and Aflibercept).
Infections and infestations Anal abscess	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.6% 3/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Fungal skin infection	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Hepatitis B	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Lung infection	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Peritonitis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Catheter site abscess	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Gastroenteritis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Herpes zoster	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.1% 2/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Lobar pneumonia	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Lung abscess	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Neutropenic sepsis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.6% 3/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Sepsis	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Urinary tract infection	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis carcinomatosa	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Neutropenia	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.8% 2/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.8% 2/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.1% 2/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Metabolism and nutrition disorders Hyperammonaemia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.1% 2/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Psychiatric disorders Completed suicide	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Psychiatric disorders Depression	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Cerebral infarction	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Peroneal nerve palsy	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Cerebral ischaemia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Loss of consciousness	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Cardiac disorders Acute left ventricular failure	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Cardiac disorders Acute coronary syndrome	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Cardiac disorders Acute myocardial infarction	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Cardiac disorders Angina pectoris	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Cardiac disorders Cardiopulmonary failure	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.53% 1/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Vascular disorders Deep vein thrombosis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.8% 2/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Vascular disorders Hypertension	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.8% 2/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Vascular disorders Subclavian vein thrombosis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.1% 2/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Vascular disorders Venous thrombosis limb	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.8% 2/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.

Other adverse events
Measure	Placebo Only n=33 participants at risk Placebo for IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Aflibercept Only n=111 participants at risk Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.	Mixed Administration (Placebo and Aflibercept) n=188 participants at risk Participants who were originally randomized to receive either Placebo or Aflibercept, actually received both the treatment (Placebo and Aflibercept).
Infections and infestations Upper respiratory tract infection	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	9.9% 11/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	10.1% 19/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Infections and infestations Urinary tract infection	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	2.7% 3/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	7.4% 14/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Neutropenia	66.7% 22/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	61.3% 68/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	71.8% 135/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Leukopenia	60.6% 20/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	53.2% 59/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	44.7% 84/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	19.8% 22/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	12.8% 24/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Blood and lymphatic system disorders Anaemia	9.1% 3/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.4% 6/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	6.4% 12/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Metabolism and nutrition disorders Decreased appetite	45.5% 15/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	37.8% 42/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	47.9% 90/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	13.5% 15/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.9% 11/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Psychiatric disorders Insomnia	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	8.1% 9/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.3% 10/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Headache	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	8.1% 9/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	9.0% 17/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Dizziness	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	7.2% 8/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	9.0% 17/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Cholinergic syndrome	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	6.3% 7/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.9% 11/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Hypoaesthesia	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	3.6% 4/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	2.7% 5/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Nervous system disorders Neuropathy peripheral	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.90% 1/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	2.1% 4/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Vascular disorders Hypertension	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	38.7% 43/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	34.6% 65/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	27.0% 30/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	20.2% 38/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	11.7% 13/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	9.6% 18/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	11.7% 13/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	13.8% 26/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Productive cough	3.0% 1/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	6.3% 7/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.6% 3/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	4.5% 5/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.9% 11/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Nausea	66.7% 22/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	55.0% 61/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	58.5% 110/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Diarrhoea	42.4% 14/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	54.1% 60/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	64.9% 122/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Vomiting	66.7% 22/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	50.5% 56/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	56.9% 107/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Stomatitis	15.2% 5/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	24.3% 27/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	31.9% 60/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Abdominal pain	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	17.1% 19/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	22.3% 42/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Constipation	24.2% 8/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	12.6% 14/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	18.6% 35/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Abdominal distension	12.1% 4/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	11.7% 13/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.9% 11/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Mouth ulceration	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	9.9% 11/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	15.4% 29/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	6.3% 7/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	8.0% 15/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.4% 6/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	2.7% 5/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Proctalgia	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.4% 6/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.6% 3/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Toothache	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.8% 2/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	1.1% 2/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Gastrointestinal disorders Rectal discharge	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Rash	9.1% 3/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	8.1% 9/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	6.9% 13/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	7.2% 8/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.3% 10/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	7.2% 8/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.9% 11/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Alopecia	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	4.5% 5/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	22.9% 43/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Pigmentation disorder	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	4.5% 5/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	3.2% 6/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	6.1% 2/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	2.7% 3/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	6.9% 13/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/33 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	0.00% 0/111 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.	5.3% 10/188 • All AE collected from signature of informed consent upto resolution/stabilization/death regardless of seriousness/relationship to IMP.After cutoff date for OS,only ongoing AE & SAE were followed until resolution,stabilization/2 follow-ups(about 4 months). Reported AEs were treatment-emergent AEs that developed/worsened during 'on-treatment period' (from first dose of Aflibercept to 30 days of follow-up visit). Safety population (subset of ITT population): all participants who received at least one dose of study drug. Due to operational treatment error, 3 arms were reported for safety analysis.