NALIRIFOX for Treatment-Naive Patients with Pancreatic Cancer

Standard chemotherapy for metastatic pancreatic cancer is either the three-drug regimen FOLFIRINOX or the two-drug combination of gemcitabine and nab-paclitaxel. The regimens had not previously been compared head-to-head in a randomized trial.

Investigators now report results of NAPOLI 3, an industry-sponsored, open-label, multinational phase 3 trial evaluating first-line treatments for metastatic pancreatic cancer. Patients were randomized to treatment with either gemcitabine/nab-paclitaxel or NALIRIFOX — a modification of FOLFIRINOX that combines continuous infusion 5-FU, oxaliplatin, and liposomal irinotecan in place of irinotecan.

Of 770 patients, 67% had two or more sites of metastasis, 80% had liver metastases, 39% had primaries in the head of the pancreas, and 94% had received no prior therapy for pancreatic cancer. At a median follow-up of 16.1 months, the primary endpoint of overall survival was superior with NALIRIFOX compared with gemcitabine/nab-paclitaxel (median, 11.1 vs. 9.2 months; hazard ratio, 0.83; P=0.036). Progression-free survival also was superior with NALIRIFOX (median, 7.4 vs. 5.6 months; HR, 0.69; P<0.0001). The objective response rate trended numerically higher with NALIRIFOX (42% vs. 36%; P=0.11). Rates of grade 3–4 serious treatment-related adverse events were similar in the two groups overall; however, diarrhea and nausea were more common with NALIRIFOX than gemcitabine/nab-paclitaxel (20% vs. 5% and 12% vs. 3%, respectively) and neutropenia and anemia were more common with gemcitabine/nab-paclitaxel than NALIRIFOX (25% vs. 14% and 17% vs. 11%, respectively).