LBA46 Bevacizumab (B) plus FOLFIRI after failure of platinum-etoposide in patients (pts) with advanced neuroendocrine carcinoma (NEC): The PRODIGE 41-BEVANEC randomized phase II study

Abstract

Platinum-etoposide combination chemotherapy is the first-line standard-of-care for pts with advanced, poorly-differentiated, gastroenteropancreatic (GEP) NEC. However, nearly all pts will develop resistance and there is no standard second-line treatment. PRODIGE 41 – BEVANEC (NCT02820857) is an academic, non-comparative, phase 2 trial. Main inclusion criteria were histologically proven, grade 3, locally advanced or metastatic GEP-NEC or NEC of unknown primary, and documented progressive disease during or after first-line therapy. Pts were randomized 1:1 to receive 5 mg/kg Bevacizumab (B) with FOLFIRI, or FOLFIRI alone, every 14 days until progression or unacceptable toxicity. The primary objective was to demonstrate a 6-month overall survival (OS) rate of ≥50% in the experimental arm (efficacy: if at least 26 of 52pts alive at 6 months), power, 85%; one-sided alpha risk, 10%). Other endpoints included progression-free survival (PFS), objective response rate (ORR), response duration, biochemical response and safety. From Sep 2017 to Feb 2022, 133 pts were randomized in 26 centers; 126 pts received at least one course of chemotherapy and were evaluable for the primary endpoint. Median age was 67 years (range 26–85), 66% males, 90% with ECOG PS 0-1. The primary tumor was mainly colorectal (n=38), pancreas (n=33), oesogastric (n=22) and unknown (=23). The primary objective was met (30 pts alive at 6 months ± 5 pts still in follow-up less than 6 months) with Folfiri-B. Median PFS and OS were 3.7 months (95%CI [1.9-5.6]) and 7.0 months (95%CI [4.6-11.5]) with Folfiri-B, and 3.5 months (95%CI [1.9-5.1]) and 8.9 months (95%CI [5.7-10.7]) with Folfiri. Biochemical response, ORR (25.5% vs 18.3%) and response duration were numerically higher in Folfiri-B vs Folfiri. Three patients stopped B because of toxicity; one treatment-related death occurred in Folfiri-B and most frequent grade ≥ 3 AEs were neutropenia (12%), asthenia (10%) and diarrhoea (10%). Folfiri-B reached the primary endpoint in 2nd line NECs pts.