Early AE Monitoring Is Key to Adjusting NALIRIFOX Dose in PDAC

Maen Abdelrahim, MD, PhD, Section Chief of Gastrointestinal Medical Oncology at Houston Methodist Neal Cancer Center in Texas, discusses how to manage the dose of NALIRIFOX (5-fluororacil, liposomal irinotecan [Onivyde], leucovorin, and oxaliplatin) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

NALIRIFOX was investigated in the NAPOLI-3 trial (NCT04083235), and follow-up analyses showed that it could remain efficacious even with dose reductions. This regimen did not show a difference in tolerability or need for dose reduction of liposomal irinotecan based on UGTA1A*28 allele status, unlike with non-liposomal irinotecan. Accordingly, Abdelrahim says that it is important to monitor for adverse events (AEs) such as diarrhea, nausea, fatigue, and anemia early and consider whether they are intolerable before deciding a dose adjustment is needed.

The first 1 to 2 cycles of treatment can give an indication of whether a patient can tolerate NALIRIFOX without dose reduction, he says. If needed, adjusting the dose can enable patients to have improved quality of life while maintaining the efficacy of the treatment.

TRANSCRIPTION:

0:10 | While we try to treat an aggressive cancer with the triplet, an aggressive regimen, we should not be having a dose adjustment earlier, before we recognize the some of the [AEs], or [before] we recognize the patient’s need for dose adjustment. This is a treatment that is supposed to have a good control and help [the] patient to live better with quality of life, but at the same time, [the] patient's profiling, their genetic makeup...metabolism of the medication might be different, so recognizing the [adverse events] of this regimen early on time will help us to maintain the patient on the regimen longer.

So it's a balance between—you don't want to decrease the dose too much, in a way that is you lose the efficacy of the treatment, but at the same time, you want to be aware of the [AEs] and adjust the doses as we go, especially in the first few cycles. [In] the first 1 to 2 cycles, you find your patient will clearly give you an indication if the dose needs to be adjusted or not. So [we should be] adjusting the dose enough to maintain efficacy…without losing much efficacy from this treatment, but helping to maintain the regimen with [fewer AEs] and maintaining quality of life.