Experience with aflibercept as a second line chemotherapy in metastatic colorectal cancer: Safety and efficacy in a real-life population

Introduction: A III-phase clinical trial has demonstrated benefit in global survival using aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer (mCRC) who progressed after being treated with oxaliplatin despite receiving previously either anti-EGFR or antiangiogenics. The main objective of our study is to analyze the benefit of this combination in the daily clinical practice and tolerance Methods: During 43 months (from March 2013 until December 2016) we treated 66 patients with FOLFIRI plus aflibercept each every 15 days as a second line chemotherapy treatment for mCRC. Efficacy and safety outcomes were analyzed. Toxicities were assessed using the Common Terminology Criteria for Adverse Events 4.3. Results: Patients median age was 58 years (28-79). All were classified as ECOG 0-1. Each patient received oxaliplatin as a first line treatment. Also prior use of bevacizumab was reported in 37 patients (56%) and anti-EGFR in 18 patients (27%). 64% of them had mutated RAS status, 33% wild-type RAS status and 3% indetermined. The median number of cycles given was 9 (1-42). Aflibercept dose reduction was required in 13% and therapy discontinuation due to toxicity was required in 18%. In all patients, some kind of grade treatment-related adverse events occurred. Most frequently 3-4 grade toxicity observed were: asthenia (13%), neutropenia (11,5%), hypertension (10%), diarrhea (8%), stomatitis (3,2%), palmar-plantar erythrodysesthesia (3,2%) and proteinuria (5%). In patients evaluable for response, the response rate was 30% and the disease control rate of 42%. The progression-free survival median time was 8 months and it was similar between prior use of bevacizumab (9 months) or not (8 months) or anti-EGFR (10 months). The overall survival median time was 16 months and it was similar between prior use of bevacizumab (16 months) or not (21 months) or anti-EGFR (22 months). There is a trend to longer OS in left colon but does not reach significance (9 vs 17 months, p = 0.1) Conclusion: In our patient series, FOLFIRI and aflibercept combination achieves a high clinical percentage benefit independently of prior therapy received. We observed efficacy with aflibercept regardless of primary tumor location, the KRAS/NRAS mutation and treatment received in first line. Observed side effects were consistent to previous III-phase trial.