Where NALIRIFOX Dose Adjustment Fits in PDAC Care

The integration of NALIRIFOX (5-fluororacil, liposomal irinotecan [Onivyde], leucovorin, and oxaliplatin) into first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC) has prompted important discussions around treatment optimization in real-world practice. The phase 3 NAPOLI-3 trial (NCT04083235) established the efficacy of NALIRIFOX compared with standard therapy, and a subsequent post hoc analysis showed that dose reductions of liposomal irinotecan and oxaliplatin did not negatively impact efficacy. Notably, tolerability and the need for dose modification of liposomal irinotecan were not affected by UGT1A1*28 allele status.

Maen Abdelrahim, MD, PhD, Section Chief of Gastrointestinal Medical Oncology at Houston Methodist Neal Cancer Center in Texas, discusses the practical considerations surrounding next-generation sequencing (NGS) testing for allele status, including challenges related to test availability, turnaround, and cost, and where dose reductions fit into the overall management of patients receiving NALIRIFOX.

He also emphasizes how flexible dosing strategies and early recognition of adverse events (AEs) can help maintain patients on NALIRIFOX while preserving both efficacy and quality of life, particularly in community practice settings where upfront testing may not always be feasible.

TRANSCRIPTION:

0:06 | This is a send-out test for most centers now. Most of the platforms that they’re doing—NGS—start reporting on UGT1A1 allele, and we start seeing the data coming about, but… [physicians often] delay the treatment until the result com[es] back. Basically, [the] patient is anxious to start treatment. So, previously, [it] has not been cost-effective to do testing and treatment based on the test because [of] the timing and the delay and the cost associated with it. So, the trend [has] been, you treat, and then based on the [AEs], you can retest.

I think now, the tests [have] become [more] readily available, and [most of the NGS] can be done in a faster format. And I think that recognizing [AEs] upfront and early for the patient will be the way to go to maintain the patient longer on the NALIRIFOX regimen.

Especially in the community, [it] is not always…a test that is routinely done. And as we mentioned…send-out test is not a test [that] can be done in your hospital or in your lab across the street from your institution. It's [only] done as send-out, and...you have to have a plan for it. So, I think having the dose reduction, recognizing [AEs], and maybe sending [the test] later on will be the way to go.