Raji Shameem, MD is a medical oncologist and hematologist at Orlando Health Cancer Institute.

Dr Shameem on Selecting NALIRIFOX vs FOLFIRINOX in Advanced Pancreatic Cancer

“When I consider dose reduction, it gives me comfort to know that I know what I'm doing is what the [NAPOLI 3] trial did, [which demonstrated] efficacy [of a given agent in a given population].”

Raji Shameem, MD, a medical oncologist and hematologist at Orlando Health Cancer Institute, discussed clinical considerations for selecting NALIRIFOX (liposomal irinotecan [Onivyde], 5-fluorouracil, leucovorin, and oxaliplatin) vs FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) for the frontline treatment of patients with advanced pancreatic cancer. 

He emphasized the importance of aligning dosing strategies with those used in pivotal trials, noting that trial-based protocols for dose reductions provide a framework that ensures treatment efficacy is maintained and minimizes the risks associated with empiric, untested modifications. Findings from the phase 3 PRODIGE 24 trial (NCT01526135), which evaluated modified FOLFIRINOX (mFOLFIRINOX) in patients with resected pancreatic adenocarcinoma, demonstrated efficacy in a relatively younger patient population, as all patients in the mFOLFIRINOX arm of this trial were younger than 80 years of age, he said. 

In contrast, the phase 3 NAPOLI-3 trial (NCT04083235) of NALIRIFOX in patients with previously untreated metastatic pancreatic cancer enrolled a broader population without age restrictions, with the oldest enrolled patient being 85 years of age, and approximately 6% of participants 75 years of age or older, he explained. According to Shameem, this distinction between the trials is particularly relevant in practice settings with a high proportion of older patients, as it provides reassurance that efficacy and safety outcomes with NALIRIFOX were observed across a more inclusive age range.

Regarding patient selection, Shameem underscored performance status as a critical determinant. He noted that although both NALIRIFOX and FOLFIRINOX are reasonable for patients with good performance status, the use of regimens composed of multiple drugs in patients with an ECOG performance status of 2 or greater may lead to excess toxicity without proportional clinical benefit. He added that this consideration is particularly important in older patients, where the balance between tolerability and efficacy must be carefully assessed.

According to Shameem, the enrollment of older adults in the NAPOLI-3 trial supports the real-world applicability of NALIRIFOX, particularly in older populations often underrepresented in pancreatic cancer trials. He stressed that chronological age should not be the sole factor guiding treatment selection and that trial data demonstrating the safety and efficacy of NALIRIFOX in older patients provide additional confidence for oncologists considering intensive regimens in this group.

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Dr Shameem on Selecting NALIRIFOX vs FOLFIRINOX in Advanced Pancreatic Cancer