Gemcitabine plus nab-paclitaxel until progression or given sequentially with 5-fluorouracile plus irinotecan (FOLFIRI.3) for first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC): A randomized phase II study (PRODIGE 37-FIRGEMAX).

Le résumé fourni par la source

4107 Background: Chemotherapy is effective in mPDAC but new approaches are still needed to improve patients (pts) survival and quality of life. We have previously published successful results of a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI regimen1 with good efficacy and tolerability results. In the present study, we tested the same sequence with the new gemcitabine + nab-paclitaxel (G+A) first-line standard therapy2. Methods: We randomized chemotherapy-naive pts with proven mPDAC, bilirubin levels ≤1.5 ULN and performance status (PS) 0-2 to receive in alternance G+A (MPACT regimen)2 (2 months [mo]) and FOLFIRI.3 (FIRGEM regimen)1 (2 mo; arm A), or G+A alone (arm B). The primary objective was to increase the 6-mo progression-free survival (PFS) rate from 40% (H0) to 60% (H1; binomial exact method; required 124 pts). Analyses were done in preplanned modified intent-to-treat (mITT, pts who received at least one dose of treatment) and per-protocol (PP, pts reaching the 2 mo treatment switch) populations. Results: Between Nov 2015 and Nov 2016, 127 pts were enrolled. Mean age was 64 years (range: 38-76), PS was 0/1/2 in 37/51/12%, no major imbalance for baseline characteristics was noted between arms. Main grade 3-4 toxicities per pt (%) were (arms A/B): diarrhea (13/2), nausea/vomiting (9/2), neutropenia (42/31), febrile neutropenia (2/0), skin toxicity (5/14), and peripheral neuropathy (13/20). No toxic deaths occurred. Best objective response rates (mITT) were A: 40% (95%CI, 28-54) and B: 25% (95%CI, 15-38). 6-mo PFS rates were A: 45% and B: 23% in mITT (n = 122; HR: 0.70; 95%CI, 0.48-1.03) and A: 60% and B: 30% in PP (n = 90; HR: 0.57; 95%CI, 0.36-0.90). Median OS (PP) was A: 15.8 and B: 12.4 mo (HR: 0.66. 95%CI, 0.37-1.16). Conclusions: The FIRGEMAX strategy with G+A followed by FOLFIRI.3 every 2 mo, appears to be feasible and effective, with manageable toxicities and decreased neurotoxicity, in patients with mPDAC able to reach > 2mo of treatment for their disease. 1-Trouilloud EJC 2014 2-Von Hoff NEJM 2013 Clinical trial information: NCT02827201.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.