NALIRIFOX Shows Survival Benefit Vs Gemcitabine/Nab-Paclitaxel in Metastatic PDAC

The phase 3 NAPOLI 3 trial (NCT04083235) enrolled 770 patients with histopathologically/cytologically confirmed untreated metastatic pancreatic ductal adenocarcinoma. Patients were given liposomal irinotecan (Onivyde) at 50 mg/m², 5-fluorouracil (5-FU) at 2400 mg/m², leucovorin at 400 mg/m², and oxaliplatin at 60 mg/m² (NALIRIFOX).

Martin F. Dietrich, MD, PhD, spoke with CancerNetwork and highlighted the trial’s positive efficacy readouts. NALIRIFOX provided an improvement in progression-free survival (PFS), with the median PFS increasing to 7.4 months in the NALIRIFOX arm compared with 5.6 months with nab-paclitaxel/gemcitabine (HR, 0.69; 95% CI, 0.58-0.83; P <.0001). The trial also showed an improvement in overall survival (OS), the primary end point, of 9.2 months in the gemcitabine/nab-paclitaxel arm vs 11.1 months in the NALIRIFOX arm (HR, 0.83; 95% CI, 0.70-0.99; P = .036). Furthermore, NALIRIFOX demonstrated a higher overall response rate of 36.2% in the gemcitabine arm vs 41.8% in the NALIRIFOX arm.

Dietrich, assistant professor of Internal Medicine at the University of Central Florida College of Medicine, and a medical oncologist at The US Oncology Network Cancer Care Centers, emphasized that this higher response rate is not only a marker of efficacy but also an important correlate for symptom relief due to tumor dimension reduction. These results show that NALIRIFOX can be considered a first-line therapeutic option for this patient population.

Transcript:

Just to start out with a little bit of an overview of NAPOLI 3. It was a global, randomized, open-label phase 3 study that evaluated NALIRIFOX, which is essentially a dose-defined triplet regimen with liposomal irinotecan, 5-FU, and leucovorin against nab-paclitaxel and gemcitabine, a standard FDA-approved regimen. It was a very large study. About 800 patients were evaluated here, with a performance status of 0 to 1. It was a very broad eligibility. We always had concerns, previously, that our data for FOLFIRINOX [leucovorin, 5-FU, irinotecan, and oxaliplatin] were age restricted, and there were other criteria that made it applicable only to a small subset of patients.

In our readouts, NALIRIFOX provided a statistically significant improvement in PFS. The median increased here from 7.4 months [for NALIRIFOX] vs 5.6 months for gemcitabine and nab-paclitaxel. When we looked at the OS, we saw an improvement from 9.2 months [in the gemcitabine arm] to 11.1 months [in the NALIRIFOX arm], and there was a higher response rate, which is important for us. We look at response rate, not only as a short-term marker of efficacy, but also as a correlate of symptom relief by reducing tumor dimensions. We saw an increase here from 36% to 41.8%, so across the board, we had better efficacy; it was obviously highly statistically significant across the different readouts for our patients.

Reference

Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023;402(10409):1272-1281. doi:10.1016/S0140-6736(23)01366-1