David Malka, Benoît Dupont, Alain Gratet, Pamela Biondiani, Marion Chauvenet, Dany Gargot, Pierre-Emmanuel Henneresse, Hortense Laharie, Johann Dreanic, Valérie Lebrun Lyat, Catherine Brezault-Bonnet, Morgan Andre, Géraldine Perkins, Philippe Houyau, Yves Rinaldi, Etienne Suc, Dominique Besson, Valérie Boige, Cécile Julien, Julien Taieb, Simon Pernot, Benoît Avisse, Pauline Regnault, Ahmed Bedjaoui, Marie-Pierre Galais, Côme Lepage, Céline Lepère, Mme E. Barbier, Antoine Holllebecque, Anne Escande, Julie Vincent, Sandrine Lavau denes, Marie-Claude Gouttebel, Leila Bengrine Lefevre, Anne Thirot Bidault, Anne-Laure Pointet, Julie Gigout, Faiza Khemissa Akouz, Louis-Marie Dourthe, Frederick Moryoussef, Maxime Lesouef, Vincent Bourgeois, François Ghiringhelli, Patrick Texereau, Samy Louafi, Gildas Phelip, Yann Berge, Jean-François Codoul, Jérôme Chamois, Eric Terrebonne, Karine Bouhier Leporrier, Bidaut Wahiba, X. Artignan, Pr Pierre Michel, Iulia Pripon, David Sefrioui, Pierre-Luc Etienne, Romain Coriat, Aurélie Parzy, Mustapha Atlassi, Aziz Zaanan, Jean-Baptiste Bachet, Philippe Dominici, Jean Martin, Mathilde Martinez, Dominique Genet, Raymond Despax, Karine Le Malicot, Laurent Miglianico, Salvatore Caruso, Bruno Valenza, Nicolas Barriere, and Oana Zveltlana Cojocarasu
Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. Results Between November 2015 and November 2016, 127 patients were enrolled. Main grade III–IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1–53.6) in arm A and 26.7% (95% CI: 16.1–39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3–56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3–32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. Conclusions The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. Trial registration information EudraCT: 2014-004449-28: NCT: 0282701.