Choosing Between Approved Frontline Metastatic Pancreatic Cancer Regimens

With 3 regimens now approved for the frontline treatment of metastatic pancreatic cancer, oncologists face an increasingly complex decision about which combination to use first, and how that choice affects a patient's options down the line. NALIRIFOX (liposomal irinotecan [Onivyde], oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) was evaluated against gemcitabine plus nab-paclitaxel (Abraxane) in the phase 3 NAPOLI-3 trial (NCT04083235). In the years since, oncologists have had to weigh those data, along with real-world evidence and post hoc exploratory analyses, against established regimens such as FOLFIRINOX (leucovorin, 5-FU, irinotecan, oxaliplatin), without a head-to-head trial directly comparing NALIRIFOX and FOLFIRINOX.

Following a Frontline Forum program, Raji Shameem, MD, and Timmy Nguyen, MD, discussed how they approach that decision in practice. Nguyen explained that the emergence of NALIRIFOX helped clarify a longstanding question about how to sequence the 3 regimens. Despite the absence of a direct comparison with FOLFIRINOX, NALIRIFOX appears at least comparably effective, with tolerability and durability of response that make it a reasonable frontline option rather than reserving more intensive regimens for later lines.

Shameem is a hematologist and medical oncologist at Orlando Health Cancer Institute, and Nguyen is a hematologist and medical oncologist at Cleveland Clinic Florida.

Transcript:

CancerNetwork: What were the themes and key takeaways from the initial conversation surrounding the latest data in metastatic pancreatic ductal adenocarcinoma (PDAC)?

Nguyen: For me, it just helped to [settle] some of the muddy water ever since NALIRIFOX came out, to see which was better of the 3 approved regimens. As always, that discussion's about how well we should save liposomal irinotecan for a later line and not use it up front and use gemcitabine plus [nab-paclitaxel] first followed by [liposomal irinotecan and 5-FU] as a salvage treatment [in the] second line. But after the discussion, we see how, even though there's no direct comparison head-to-head with FOLFIRINOX, NALIRIFOX compared with all 3 seems to be…as good as FOLFIRINOX, if not better, because of its tolerability and efficacy with the long-term sustained [response]. Some patients can't go to the second line, so it's good to use the best treatment up front.

Shameem: That's a really good point. I think we discussed that—you brought that up as well during the discussion—your first shot is typically your best shot. Even in NAPOLI-3, in a well-conducted clinical trial, about 50% or more patients never saw a second-line therapy, and that's how I've incorporated it in my practice, too. I feel that there's no guarantee for subsequent therapies. We know the treatment landscape is evolving. I'm sure we're going to talk about RAS inhibition, but a lot of our patients only really get 1 line of therapy; as we know, pancreatic cancer can be quite devastating. I totally agree with your conclusion from that discussion.

Reference

Hussein MA, Khan G, Chandana SR, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): updated overall survival analysis with 29-month follow-up of NAPOLI 3. J Clin Oncol. 2024;42(suppl 16):4136. doi:10.1200/JCO.2024.42.16_suppl.4136