Adding aflibercept to first-line mFOLFOX6 (fluorouracil, leucovorin, oxaliplatin) did not improve progression-free survival compared with mFOLFOX6 alone in patients with metastatic colorectal cancer (mCRC) and the combination was associated with higher toxicity, a study published in the journal Annals of Oncology has shown.1
Because the combination of aflibercept with FOLFIRI (fluorouracil, leucovorin, irinotecan) has resulted in significantly improved overall survival in patients with mCRC who have progressed on oxaliplatin-based therapy, researchers sought to evaluate the addition of aflibercept to first-line oxaliplatin-based chemotherapy.
For the phase 2 AFFIRM trial, researchers enrolled 236 patients with mCRC. Participants were randomly assigned to receive first-line therapy with mFOLFOX6 plus aflibercept 4 mg/kg or mFOLFOX6 alone.
Results showed that the 12-month progression-free survival rates were 25.8% (95% CI, 17.2-34.4) for aflibercept plus mFOLFOX6 and 21.2% (95% CI, 12.2-30.3) for mFOLFOX6 alone. Median progression-free survival was 8.48 months (95% CI, 7.89-9.92) and 8.77 months (95% CI, 7.62-9.27), respectively (HR, 1.00; 95% CI, 0.74-1.36).
In the combination arm, 49.1% (95% CI, 39.7-58.6) of patients achieved a response compared with 45.9% (95% CI, 36.4-55.7) without aflibercept.
With respect to safety, the most common treatment-emergent grade 3 or 4 adverse events were neutropenia (36.1% for aflibercept-mFOLFOX6 vs 29.3% for mFOLFOX6), neuropathy (16.8% vs 17.2%), and diarrhea (13.4% vs 5.2%).
The aflibercept arm was also associated with higher rates of hypertension, proteinuria, deep vein thrombosis, and pulmonary embolism.
1. Folprecht G, Pericay C, Saunders MP, et al. Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first line treatment of patients with metastatic colorectal cancer – the AFFIRM study [published online ahead of print April 18, 2016]. Ann Oncol. doi:10.1093/annonc/mdw176.