Oxaliplatin–Fluoropyrimidine Chemotherapy Plus Bevacizumab in Advanced Neuroendocrine Tumors

OBJECTIVES: This study aimed to determine the safety and effectiveness of bevacizumab (B) plus FOLFOX or CAPOX in advanced neuroendocrine tumors (NETs) by performing a combined analysis of 2 separate prospective phase II studies. METHODS: In the FOLFOX/B study, patients received chemotherapy without scheduled breaks in 3 cohorts: carcinoid, pancreatic NET, and poorly differentiated neuroendocrine carcinomas. In the CAPOX/B study, NET subtypes were pooled, and patients were treated with 4 cycles of CAPOX/B followed by optional maintenance therapy. Primary end points were radiographic response rate (RR) after 12 cycles (FOLFOX/B), progression-free survival (PFS) (CAPOX/B), and toxicity (both). RESULTS: Seventy-six patients (FOLFOX/B, n = 36; CAPOX/B, n = 40) were included. In FOLFOX/B, RR for carcinoid at 12 cycles 3/22 (13.6%), median PFS 19.3 months; RR for pancreatic NET at 12 cycles 4/12 (41.7%), median PFS 21 months; RR 1/2 (50%) in poorly differentiated neuroendocrine carcinoma; pooled RR 25% and median PFS 21 months (1-year PFS 68%). In CAPOX/B (pooled NET), RR 18% and median PFS 16.7 months (1-year PFS 65%). Predictable toxicity was observed. CONCLUSIONS: Neither study met its primary end point, but radiographic responses and prolonged disease stability in previously progressing patients suggest that selected patients with NET may benefit from oxaliplatin-fluoropyrimidine chemotherapy plus bevacizumab and that the combination may warrant further study.