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

Background

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.

Methods

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.

Results

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%).

Conclusions

Folfiri-B reached the primary endpoint in 2nd line NECs pts.

Clinical trial identification

NCT02820857.

Editorial acknowledgement

Legal entity responsible for the study

Thomas Walter.

Funding

ROCHE has furnished the bevacizumab for the experimental arm.

Disclosure

T.A. Walter: Non-Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Invited Speaker: Novartis-AAA, Ipsen. R. Coriat: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Funding: Ipsen. D. Malka: Financial Interests, Personal, Invited Speaker: Roche. F. Di Fiore: Financial Interests, Personal, Invited Speaker: Merck, Roche, Pierre Fabre, Ipsen, Novartis, Sanofi, Bayer, Servier. V. Hautefeuille: Financial Interests, Personal, Invited Speaker: Novartis-AAA; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Principal Investigator: Ipsen. V. granger: Financial Interests, Personal, Invited Speaker: AAA-Novartis; Financial Interests, Personal, Advisory Board: Mylan. L. Mineur: Financial Interests, Personal and Institutional, Invited Speaker: Amgen, Servier; Financial Interests, Institutional, Research Grant: haliodx; Non-Financial Interests, Personal, Other, Congress travel: Merck, Ipsen. C. Lepage: Financial Interests, Personal, Invited Speaker: Ipsen, Amgen; Financial Interests, Personal, Advisory Board: Novartis. All other authors have declared no conflicts of interest.