Dr Wainberg on Frontline Chemotherapy Selection in Pancreatic Cancer

“There is a lot of confusing information, and [we do not have] a lot of phase 3 trials [comparing any of these 3 regimens head-to-head], except for the NAPOLI-3 trial.”

Zev A. Wainberg, MD, a professor of medicine and co-director of the UCLA GI Oncology Program at the University of California, Los Angeles, discussed prominent frontline chemotherapy regimens for patients with metastatic pancreatic cancer, such as, NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil [5-FU], and leucovorin), FOLFIRINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin), and gemcitabine plus nab-paclitaxel (Abraxane), as well as data from the phase 3 NAPOLI-3 study (NCT04083235), which compared NALIRIFOX vs gemcitabine plus nab-paclitaxel.

Wainberg began by laying out the standards for palliative chemotherapies in the metastatic setting for pancreatic cancer. Wainberg noted that historically, there have been 2 palliative chemotherapy regimen options for patients: modified FOLIRINOX and gemcitabine plus nab-paclitaxel. However, data from NAPOLI-3 supported the FDA approval of NALIRIFOX in February 2024, adding to the pool of available regimens, Wainberg said.

In the randomized trial, NALIRIFOX demonstrated significant efficacy improvements over gemcitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma (n = 770). Patients who received NALIRIFOX (n = 383) achieved a median overall survival of 11.1 months (95% CI, 10.0-12.1) compared with 9.2 months (95% CI, 8.3-10.6) for patients who received gemcitabine/nab-paclitaxel (n = 387; HR, 0.84; 95% CI, 0.71-0.99; P = .0403). Moreover, progression-free survival (PFS) outcomes favored NALIRIFOX, with patients in the NALIRIFOX arm experiencing a median PFS of 7.4 months (95% CI, 6.0-7.7) compared with 5.6 months (95% CI, 5.3-5.8) for the gemcitabine/nab-paclitaxel arm (HR, 0.70; 95% CI, 0.59-0.85; P = .0001).. Objective response rates (ORR) were also improved, with respective ORRs of 41.8% (95% CI, 36.8%-46.9%) and 36.2% (95% CI, 31.4%-41.2%) for the NALIRIFOX and gemcitabine/nab-paclitaxel arms.

However, Wainberg mentioned NAPOLI 3 is the only randomized, phase 3 trial with head-to-head data for any of these chemotherapy regimens. Wainberg explained how FOLFIRINOX is similar to NALIRIFOX, and that in other trials have shown virtually no differences in efficacy between gemcitabine/nab-paclitaxel and FOLFIRINOX.

Ultimately, Wainberg concluded by acknowledging how the conflicting data from different trials can be confusing in terms of informing frontline chemotherapy decisions, noting that other factors like toxicity and patient goals and characteristics can help inform this decision.