Additional OS and PFS Benefits With Aflibercept in Post-Hoc VELOUR Analysis

A post-hoc analysis of the VELOUR trial demonstrated additional improvements in both overall survival (OS) and progression-free survival (PFS) in favor of aflibercept plus FOLFIRI in patients with metastatic colorectal cancer (mCRC). The analysis was presented at the European Cancer Congress 2013 (ECCO-ESMO-ESTRO), held September 27 to October 1 in Amsterdam, The Netherlands.

The VELOUR trial of aflibercept plus FOLFIRI versus FOLFIRI plus placebo was designed to include important subgroups of patients with mCRC encountered in the second-line setting, including those who had received prior bevacizumab therapy. VELOUR also included patients who progressed rapidly (<6 months) following adjuvant treatment with oxaliplatin—one of the few phase III trials to do so. The post-hoc analysis of the intent-to-treat (ITT) population excluded these rapid adjuvant progressors. The analysis also found improvements in both OS and PFS regardless of whether or not patients had been exposed to prior bevacizumab therapy.

According to the authors of the posthoc analysis, rapid adjuvant progressors are usually refractory to any subsequent therapy and have an extremely poor prognosis, thus negatively affecting outcomes regardless of the treatment received. Despite this, an incremental increase in OS of 1.4 months was observed with aflibercept compared with placebo in the overall &ldquo;all-takers&rdquo; second-line VELOUR population. A total of 1226 patients were included in the overall VELOUR ITT population.

Of these, 186 in the aflibercept/FOLFIRI arm had received prior bevacizumab as had 187 of the placebo controls. A total of 17 patients in the prior bevacizumab arm were rapid adjuvant progressors, 9 of them having been randomized to aflibercept and the remaining 8 to placebo. Among patients who had not received prior bevacizumab, 426 and 427 had been randomized to aflibercept vs placebo, respectively. Fifty-one patients randomized to aflibercept, and 56 randomized to placebo within the non-bevacizumab subgroup were rapid adjuvant progressors. All rapid adjuvant progressors were excluded from the current post-hoc analysis.

&ldquo;As expected, when rapid adjuvant progressors were excluded from the overall ITT population, a 1.9-month incremental benefit was observed with aflibercept over placebo&hellip;demonstrating a 22.1% relative risk reduction for death,&rdquo; the authors observed. &ldquo;These findings reinforce the benefit of aflibercept treatment in clinically relevant populations of mCRC patients, including those with prior bevacizumab use.&rdquo;