Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen

Overall Survival was the time interval from the date of randomization to the date of death due to any cause. Once disease progression was documented, participants were followed every 2 months for survival status, until death or until the study cutoff date, whichever came first. The final data cutoff date for the analysis of OS was the date when 863 deaths had occurred (07 February 2011). OS was estimated using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.

Time frame: From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)

Population: Intent-to-treat population (ITT) - all participants who gave informed consent and were randomized.

Serum samples for immunogenicity assessment were analyzed using a bridging immunoassay to detect ADA. Positive samples in the ADA assay were further analyzed in the NAb assay using a validated, non-quantitative ligand binding assay.

Time frame: Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo

Population: Immunogenicity population included all participants who were treated and tested for immunogenicity at least once post-baseline.

All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 30 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.

Time frame: From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized

Population: The safety population was the subset of the ITT population that took at least one dose of study treatment. Analyses was based on the treatment actually received (any participant who received at least one dose of aflibercept, even when receiving the rest of study treatment with placebo, was counted in the aflibercept treatment arm).

The overall ORR was the percentage of evaluable participants who achieved complete response \[CR\] or partial response \[PR\] according to RECIST criteria version 1.0. * CR reflected the disappearance of all tumor lesions (with no new tumors) * PR reflected a pre-defined reduction in tumor burden Tumors were assessed by the IRC using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks.

Time frame: From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months)

Population: The evaluable patient population (EPP) for tumor response included all randomized participants with measurable disease at study entry, as per IRC evaluation, and with at least one valid post-baseline tumor evaluation.

PFS was the time interval from the date of randomization to the date of progression, or death from any cause if it occurs before tumor progression is documented. To evaluate disease progression, copies of all tumor imaging sets were systematically collected and assessed by the IRC. PFS was analyzed using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model. The analysis for PFS was performed as planned when 561 deaths (OS events) had occurred.

Time frame: From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months)

Population: Intent to Treat (ITT) population included all participants who gave informed consent and were randomized.