FOLFIRINOX Not Better Than Gemcitabine-Cisplatin in Biliary Cancer

Standard chemotherapy agents for advanced biliary cancer are gemcitabine and cisplatin. Recent data suggest a modest benefit for use of second-line FOLFOX. Interest in three-drug regimens has been supported in pancreaticobiliary cancers based on use of first line FOLFIRINOX in pancreatic cancer.

Investigators now report results of the PRODIGE 38 AMEBICA study, an open-label, multicenter, phase 2/3 trial comparing first-line treatment of advanced biliary cancer with modified FOLFIRINOX or gemcitabine-cisplatin. Of 190 patients randomized, most had intrahepatic primaries (62%–64%) followed by extrahepatic (19%–21%) and gallbladder (17%–18%). A minority had prior surgery (17%–25%) and most had liver or liver plus extrahepatic disease (71%–85%).

The primary phase 2 endpoint — ≥73% progression-free survival (PFS) at 6 months with mFOLFIRINOX in the intention to treat population — was not reached, with a PFS of 44.6%. PFS at 6 months with gemcitabine-cisplatin was similar (47.3%). Median PFS and overall survival (OS) were similar in the mFOLFIRINOX and gemcitabine-cisplatin groups (PFS, 6.2 and 7.4 months; OS, 11.7 and 13.8 months), with gemcitabine-cisplatin trending better. Similar results were observed in the per protocol population. Response rates were also similar for mFOLFIRINOX and gemcitabine-cisplatin (25.0% and 19.4%). Rates of grade 3/4 fatigue, diarrhea, neuropathy, and anorexia were higher with mFOLFIRINOX and neutropenia was higher with gemcitabine-cisplatin.