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

Abstract

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.

• Authors: Jean Marc Phelip, Jérôme Desrame, Julien Edeline, Emilie Barbier, Eric Terrebonne, Pierre Michel, Hervé Perrier, Laetitia Dahan, Vincent Bourgeois, Faiza Khemissa Akouz, Emilie Soularue, Valérie Lebrun Ly, Yann Molin, Thierry Lecomte, François Ghiringhelli, Romain Coriat, Samy Louafi, Cindy Neuzillet, Sylvain Manfredi, David Malka, PRODIGE 38 AMEBICA Investigators/Collaborators
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 40 Issue 3 Pg. 262-271 (01 20 2022) ISSN: 1527-7755 [Electronic] United States
• PMID: 34662180 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• folfirinox
• Oxaliplatin
• Deoxycytidine
• Irinotecan
• Cisplatin
• Leucovorin
• Fluorouracil
• Gemcitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biliary Tract Neoplasms (drug therapy, mortality, pathology)
• Cisplatin (adverse effects, therapeutic use)
• Deoxycytidine (adverse effects, analogs & derivatives, therapeutic use)
• Disease Progression
• Female
• Fluorouracil (adverse effects, therapeutic use)
• France
• Humans
• Irinotecan (adverse effects, therapeutic use)
• Leucovorin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Neoplasm Metastasis
• Oxaliplatin (adverse effects, therapeutic use)
• Progression-Free Survival
• Time Factors
• Gemcitabine