Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

Chemotherapy with FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves survival in patients with previously treated metastatic colorectal cancer (mCRC). Our phase II study evaluated efficacy and tolerability of this treatment in non-pretreated patients with mCRC. Though the primary endpoint was not met, results showed that first line FOLFIRI + aflibercept for mCRC leads to survival close to those reported with standard first-line treatments, but with significant toxicities. Background: FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) thorn aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line. Patients and Methods: Patients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H-0: 55% and H-1 = 75%. Data were analyzed in intention to treat. Results: Forty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had > 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI thorn aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification. Conclusion: Although the primary objective was not met, first-line FOLFIRI thorn aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction. (C) 2020 Published by Elsevier Inc.