Aflibercept Plus FOLFIRI vs. Placebo Plus FOLFIRI in Second-Line Metastatic Colorectal Cancer: a Post Hoc Analysis of Survival from the Phase III VELOUR Study Subsequent to Exclusion of Patients who had Recurrence During or Within 6 Months of Completing Adjuvant Oxaliplatin-Based Therapy

Abstract

The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6 months of completion of oxaliplatin-containing adjuvant chemotherapy (N = 124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population (N = 1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population (N = 1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95 % confidence interval (CI) 0.68-0.90; median survival difference 1.87 months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95 % CI 0.63-1.04; median survival difference 2.14 months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-naïve patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns.

Utility of Serial Transcriptomic Analyses to Characterize the Resistome and to Refine Treatment Selection for Metastatic Colon Cancer: Case Report

“…Though VEGFD has also emerged as a resistance factor to bevacizumab benefit in colon cancer patients, [10] it was not present in this case. Though zivaflibercept which impedes both VEGFA and VEGFB was found to produce similar benefits compared to bevacizumab for the general population of metastatic colon cancer patients, [11,12] the expression profile of VEGFA, VEGFB, and KDR in this case favors ziv-aflibercept rather than bevacizumab.…”

Second-line targeted therapy for metastatic colorectal cancer. Possibilities for choices

“…или более 9 мес.) [16], но не после адъювантной ХТ [17], а также независимо от предшествующей терапии бевацизумабом. А группа максимальной эффективности представлена больными при статусе ECOG 0 и любом числе зон метастазирования или ECOG 1 и наличии не более 2 зон метастатического поражения [18].…”

Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

“…A phase III randomized trial that used Aflibercept plus a combination of fluorouracil, leucovorin and irinotecan (called FOLFIRI) found a significant increase in overall and progression free survival relative to placebo plus FOLFIRI in metastatic colorectal cancer (mCRC) patients that had been previously treated with oxaliplatin, the effects were also significant in patients that were previously treated with bevacizumab [ 44 ]. Currently, at least nine clinical trials that use Aflibercept are recruiting patients [ 45 , 46 , 47 ].…”