NALIRIFOX Regimen As First-Line Therapy for Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Sensitivity Analysis From Phase 3 NAPOLI 3 Trial

At the 2023 World Congress on Gastrointestinal Cancers, Zev Wainberg, MD, David Geffen School of Medicine at University of California-Los Angeles, California, presents data from the phase 3 NAPOLI 3 study, evaluating the NALIRIFOX chemotherapy regimen in the first-line setting for patients with metastatic pancreatic ductal adenocarcinoma.

Results from this study support the use of NALIRIFOX as a new reference regimen for the first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma.

Transcript:

Hi, I am Dr. Zev Wainberg, GI medical oncologist from UCLA, Los Angeles, California, and at the 2023 World Congress on Gastrointestinal Cancers, we updated the NAPOLI-3 phase 3 clinical trial. Just as a reminder, this was a very large global randomized phase 3 trial, which enrolled patients with newly diagnosed metastatic pancreatic cancer and randomized them to either of the investigational arm, which was NALIRIFOX, a combination of 5-FU/leucovorin and oxaliplatin and liposomal irinotecan with slightly modified doses compared to FOLFIRINOX versus the control arm, which was gemcitabine and nab-paclitaxel, which was utilized as standard dosing. The primary end point of the study was overall survival with secondary end points including progression-free survival and response rate.

At this Congress, we updated several of the analyses that have been performed, primarily looking at overall survival, which was improved in the investigational arm of NALIRIFOX at 11.1 months versus gemcitabine plus nab-paclitaxel, which was 9.2 months, and an improvement of approximately 2 months of overall survival. The progression-free survival also met its end points having improved also by about 2 months.  Those data were consistent with data that was presented prior and also met all statistical significance with respect to hazard ratios and P-value. The response rate was also numerically improved from 36% to about 42%, although that was not statistically significant.

The study also updated a few other variables, including some toxicity data that really demonstrated what we knew, which is that the toxicity profile was different. NALIRIFOX had more GI toxicity, and the gemcitabin plus nab-paclitaxel had more cytopenias and actually more peripheral neuropathy as well. One of the recent updates to the dataset included the data that includes at progression what happens, with the idea being if we can isolate the impact of frontline therapy, and the way to do that is to control for the patients that get censored at the point of progression. This censoring at the point of progression did take place in this analysis, and that analysis really did suggest that the benefits of NALIRIFOX were maintained over gemcitabine plus nab-paclitaxel, which really points to the limited impact of the second-line therapy on long-term overall survival. This all reinforces the concept that the frontline therapy that matters the most during that and the frontline therapy in this context was NALIRIFOX, which did show all of the relevant improvements over gemcitabine plus nab-paclitaxel.

This data is presented today at this 2023 World Congress on Gastrointestinal Cancers, and has been accepted for publication in Lancet, which will be published very shortly. Thank you.

Source:

Wainberg Z, Melisi D, Macarulla T, et al. Liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma: Sensitivity analysis of survival from the NAPOLI 3 trial. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-1