(ChemotherapyAdvisor) – Combining the recombinant fusion protein aflibercept (also known as ziv-aflibercept) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC) resistant to oxaliplatin, investigators reported in the Journal of Clinical Oncology online September 4.

“Aflibercept, which prevents VEGFA, VEGFB, and PlGF from binding to their receptors, is the first agent to demonstrate a survival benefit in patients previously treated with an oxaliplatin-based regimen who are being treated with FOLFIRI for their metastatic disease,” Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg, Leuven, Belgium, and colleagues noted.

The phase III trial randomly assigned patients to receive aflibercept 4mg/kg IV (n=612) or placebo (n=614) every 2 weeks in combination with FOLFIRI. At a median follow-up of 22.3 months, patients in the aflibercept plus FOLFIRI arm had a significantly improved OS, the primary end point, compared with placebo plus FOLFIRI (HR 0.817; 95.34% CI, 0.713–0.937; P=0.0032). Median survival was 13.5 months in the combination arm vs 12.1 months in the placebo arm.

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Aflibercept plus FOLFIRI also significantly improved progression-free survival (PFS; HR 0.758; 95% CI, 0.661–0.869; P<0.0001); median PFS was 6.9 vs 4.7 months, respectively.

“The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients,” they wrote. “Response rate was 19.8% (95% CI, 16.4%–23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5%–13.8%) with placebo plus FOLFIRI (P=0.0001).”

Antivascular EGFR-related adverse effects were observed with aflibercept combined with FOLFIRI and an increased incidence of some chemotherapy-related toxicities were also found.

“Aflibercept plus FOLFIRI may provide a new therapeutic option for the treatment of mCRC in patients previously treated with oxaliplatin,” they concluded.