Dr O'Reilly on Survival Outcomes of the NAPOLI 3 trial in Metastatic PDAC

Eileen M. O'Reilly, MD, gastrointestinal oncologist, Winthrop Rockefeller Endowed Chair of Medical Oncology, co-director, Medical Initiatives, David M. Rubenstein Center for Pancreatic Cancer Research, section head, Hepatopancreaticobiliary & Neuroendocrine Cancers, Memorial Sloan Kettering Cancer Center, discusses survival outcomes from the phase 3 NAPOLI 3 trial (NCT04083235) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

At the 2023 ASCO Annual Meeting, O’Reilly and colleagues presented updated data from the phase 3 trial, which demonstrated that treatment with NALIRIFOX—liposomal irinotecan (Onivyde) plus 5-fluorouracil (5-FU), leucovorin, and oxaliplatin—led to a median overall survival (OS) of 11.1 months (95% CI, 10.0-12.1) compared with 9.2 months (95% CI, 8.3-10.6) for nab-paclitaxel (Abraxane) plus gemcitabine (HR, 0.83; 95% CI, 0.70-0.99; P = .04). The 12- and 18-month OS rates were 45.6% (95% CI, 40.5%-50.5%) and 26.2% (95% CI, 20.9%-31.7%) for NALIRIFOX, respectively, compared with 39.5% (95% CI, 34.6%-44.4%) and 19.3% (95% CI, 14.8%-24.2%) for nab-paclitaxel/gemcitabine, respectively.

Additionally, NALIRIFOX elicited an objective response rate (ORR) of 41.8% (95% CI, 36.8%-46.9%) vs 36.2% (95% CI, 31.4%-41.2%) for nab-paclitaxel/gemcitabine.

Previous findings presented at the 2023 Gastrointestinal Cancers Symposium also showed that first-line treatment with NALIRIFOX produced a clinically meaningful and statistically significant improvement in OS and PFS vs nab-paclitaxel plus gemcitabine. The updated results shared at the 2023 ASCO Annual Meeting built upon these previous outcomes, O'Reilly explains.

When examining these updated results at 12 and 18 months, the outcomes held up in favor of NALIRIFOX compared with nab-paclitaxel plus gemcitabine, O'Reilly expands. Moreover, no matter which time point that an investigator looked at, the outcomes on the NALIRIFOX arm were better relative to nab-paclitaxel plus gemcitabine, supporting the initial results of the study, she says. Although NALIRIFOX produced numerically more responses compared with nab-paclitaxel/gemcitabine, the vast majority of responses in both arms were partial responses, O’Reilly adds.

There was also a longer duration on treatment in the NALIRIFOX arm, O’Reilly continues. As of the July 2022 data cutoff, there were more patients remaining on the study in the NALIRIFOX arm compared with gemcitabine/nab-paclitaxel, O’Reilly concludes.