Jean Marc Phelip1, Jérôme Desrame2, Julien Edeline3, Emilie Barbier4, Eric Terrebonne5, Pierre Michel6, Hervé Perrier7, Laetitia Dahan8, Vincent Bourgeois9, Faiza Khemissa Akouz10, Emilie Soularue11, Valérie Lebrun Ly12, Yann Molin13, Thierry Lecomte14, François Ghiringhelli15, Romain Coriat16, Samy Louafi17, Cindy Neuzillet18, Sylvain Manfredi19, David Malka20. 1. INSERM U1059, Université Jean Monnet, CHU de Saint Etienne, Hôpital Nord, Saint-Etienne, France. 2. Hôpital privé Jean Mermoz, Lyon, France. 3. Centre Eugène Marquis, Rennes, France. 4. FFCD, EPICAD INSERM LNC-UMR 1231, Dijon, France. 5. Hôpital Haut-Lévêque, Pessac, France. 6. CHU Charles Nicolle, Rouen, France. 7. Hôpital Saint Joseph, Marseille, France. 8. CHU la Timone, Marseille, France. 9. Hôpital Duchenne, Boulogne sur mer, France. 10. CH Perpignan, Perpignan, France. 11. Hôpital de Bicêtre, le Kremlin Bicêtre, France. 12. CHU Dupuytren, Limoges, France. 13. Clinique de La Sauvegarde, Lyon, France. 14. Hôpital Trousseau, Tours, France. 15. Centre Georges-François Leclerc, Dijon, France. 16. CHU Cochin, Paris, France. 17. Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France. 18. Curie Institute, Saint Cloud, France. 19. INSERM U1231, Université Bourgogne, Franche Comté, CHU Le Bocage, Dijon, France. 20. Gustave Roussy, Université Paris Saclay, Villejuif, France.
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.
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: Felix Thol; Simon Johannes Gairing; Carolin Czauderna; Thomas Thomaidis; Thomas Gamstätter; Yvonne Huber; Johanna Vollmar; Johanna Lorenz; Maurice Michel; Fabian Bartsch; Lukas Müller; Roman Kloeckner; Peter Robert Galle; Marcus-Alexander Wörns; Jens Uwe Marquardt; Markus Moehler; Arndt Weinmann; Friedrich Foerster Journal: JHEP Rep Date: 2021-12-16
Authors: Aurelie Tomczak; Christoph Springfeld; Michael T Dill; De-Hua Chang; Daniel Kazdal; Ursula Wagner; Arianeb Mehrabi; Antje Brockschmidt; Tom Luedde; Patrick Naumann; Albrecht Stenzinger; Peter Schirmacher; Thomas Longerich Journal: Br J Cancer Date: 2022-08-19 Impact factor: 9.075