Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study.

Purpose: Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown.
Methods: In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected).
Results: A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one).
Conclusion: mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
Competing Interests: Jean marc PhelipHonoraria: Merck Serono, Roche, Sanofi, Amgen, Lilly, Servier, BayerConsulting or Advisory Role: Roche, Merck Serono, Amgen, Servier, Bayer, SanofiResearch Funding: Roche, Merck SeronoTravel, Accommodations, Expenses: Roche, Merck Serono, Bayer, Servier, Sanofi Jérôme DesrameExpert Testimony: RocheTravel, Accommodations, Expenses: Hospira Julien EdelineConsulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, Ipsen, AstraZeneca, MSD, AstraZeneca, Eisai, Boston Scientific, AstraZeneca, Roche, Basilea, AstraZeneca, Merck SeronoResearch Funding: Bristol Myers Squibb, BeigeneTravel, Accommodations, Expenses: Amgen, Bristol Myers Squibb, Roche Eric TerrebonneConsulting or Advisory Role: Ipsen, Servier Pierre MichelHonoraria: Bayer, Servier Laetitia DahanHonoraria: Amgen, BMS, Servier, Oseus, Mylan Vincent BourgeoisConsulting or Advisory Role: ServierTravel, Accommodations, Expenses: Servier, Sanofi Faiza Khemissa AkouzLeadership: Bayer, SanofiTravel, Accommodations, Expenses: Sanofi, Ipsen, Servier, Roche Emilie SoularueConsulting or Advisory Role: ServierSpeakers' Bureau: BMSTravel, Accommodations, Expenses: Servier Yann MolinConsulting or Advisory Role: Janssen Oncology Thierry LecomteConsulting or Advisory Role: Sanofi, Merck Serono, Servier, Amgen, Sanofi, Amgen, Ipsen, Pierre FabreTravel, Accommodations, Expenses: Ipsen, Servier/Pfizer François GhiringhelliHonoraria: RocheTravel, Accommodations, Expenses: Amgen, Roche/Genentech Romain CoriatConsulting or Advisory Role: BayerSpeakers' Bureau: Novartis/Ipsen, Bayer, AmgenResearch Funding: IpsenTravel, Accommodations, Expenses: Pierre Fabre, Amgen Cindy NeuzilletHonoraria: Servier, Roche, AstraZeneca, Bristol Myers Squibb, Amgen, Merck¸ MSD Oncology, Novartis, Pierre Fabre, Incyte, Mylan, Baxter, Fresenius Kabi, NutriciaResearch Funding: Roche, AstraZeneca, OSE ImmunotherapeuticsTravel, Accommodations, Expenses: MSD Oncology, Merck, Amgen, Mylan David MalkaHonoraria: Roche, Bayer, Servier, Sanofi, HalioDx, Pierre Fabre, Viatris, Bristol Myers Squibb, MSD Oncology, LEO PharmaConsulting or Advisory Role: Roche, Sanofi, Merck Serono, MSD, Servier, Bayer, Incyte, Amgen, HalioDx, Agios, Bristol Myers SquibTravel, Accommodations, Expenses: Roche, Bayer, Sanofi, Merck Serono, Servier, AmgenNo other potential conflicts of interest were reported.