Study of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer

PFS rate at 12 months was defined as the percentage of patients alive without disease progression at 12 months after randomization. The primary efficacy analysis was based on assessment by the Independent Review Committee (IRC). The study was not powered for comparison of PFS rate at 12 months between the two arms (non-comparative, open-label study). Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.

Time frame: 12 months

Population: Analyses of PFS rate was performed in the evaluable patient (EP) population as the primary analysis population. Overall, 9 patients from the randomized population were excluded from the EP population.

The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.

Time frame: Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status

Population: Participants treated with aflibercept and evaluable for antibody assessment.

Summary of treatment-emergent adverse events in the safety population. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used in this study to grade the severity of AEs.

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: Of the total 235 patients included in the safety population, 116 patients received mFOLFOX6 and 119 patients received mFOLFOX6 + aflibercept. One patient, randomly assigned to the mFOLFOX6 arm did not receive any study treatment and was therefore excluded from the safety analyses.

Summary of overall objective response rate based on tumor assessment by the Independent Review Committee (IRC) as per Response Evaluation Criteria in Solid Tumours (RECIST) criteria. ORR was defined as the proportion of patients with confirmed Complete Response (CR) or confirmed Partial Response (PR) relative to the total number of patients in the analysis population. Per RECIST v 1.0 target lesions evaluation and assessed by tumor imaging: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): \>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The study was not powered for comparison of ORR between the two arms (non-comparative, open-label study).

Time frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)

Population: Evaluable Patient population.

Overall survival was defined as the time from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earliest between the last date the patient was known to be alive and the study cutoff date. The study was not powered for comparison of OS between the two arms (non-comparative, open-label study).

Time frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)

Population: Intent-to-treat population (ITT) - all participants who gave informed consent and were randomized. Of the 268 screened participants, 236 were randomly assigned to treatments, whereas 32 participants were screen failures.

PFS was defined as the time from the date of randomization to the date of tumor progression or death from any cause, whichever occurred first. PFS was based on tumor assessment by the Independent Review Committee (IRC). PFS was estimated from Kaplan-Meier Curves. The study was not powered for comparison of PFS between the two arms (non-comparative, open-label study). Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.

Time frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)

Population: Evaluable patient (EP) population. A total of 55 patients (32 in the mFOLFOX6 group and 23 in the mFOLFOX6 + aflibercept group) were without an event at the cutoff date for the PFS analysis by IRC.