Can first-line NALIRIFOX emerge victorious against Gem+NabP (Gemcitabine + Nab-paclitaxel) in patients with mPDAC?

NALIRIFOX for Metastatic Pancreatic Ductal Adenocarcinoma

Liposomal irinotecan in combination with 5-fluorouracil/leucovorin (5-FU/LV) is already approved for the treatment of mPDAC after progression on gemcitabine-based therapy in the United States and Europe.

The NALIRIFOX regimen significantly improved overall survival and progression-free survival versus nab-paclitaxel plus gemcitabine in the Phase III NAPOLI-3 trial in previously untreated patients with metastatic pancreatic cancer. NALIRIFOX includes the active ingredients liposomal irinotecan, fluorouracil, leucovorin, and oxaliplatin. The NALIRIFOX regimen was investigated in 770 previously untreated patients with metastatic pancreatic ductal adenocarcinoma in an open-label randomized study. Patients were randomly assigned to receive either the NALIRIFOX regimen or conventional treatment. On days 1 and 15 of a 28-day cycle, liposomal irinotecan at 50 mg/m2 was coupled with fluorouracil at 2,400 mg/m2, leucovorin at 400 mg/m2, and oxaliplatin at 60 mg/m2. On days 1, 8, and 15 of a 28-day cycle, the control regimen included 125 mg/m2 nab-paclitaxel and 1,000 mg/m2 gemcitabine.

According to the results presented at the ASCO 2023 conference, the median OS in the NALIRIFOX group was 11.1 months against 9.2 months in the Gem+NabP group; the median PFS was 7.4 months versus 5.6 months. In patients who received NALIRIFOX or Gem+NabP, the median (95% CI) duration of response was 7.3 (5.8-7.6) months and 5.0 (3.8-5.6) months, respectively. 

In the updated results, mDOR of 7.3 months was observed in patients being administered NALIRIFOX as compared to an mDOR of 5 months in patients who were administered the Gem + NabP combination.

As far as the safety profile is concerned, serious treatment-emergent adverse events (TEAEs) were recorded in 54.3% of NALIRIFOX patients and 51.5% of gemcitabine/nab-paclitaxel patients. TEAEs of grade 3 or above were recorded in 87.0% and 86.0% of the cases, respectively. TEAEs that resulted in mortality were recorded in 5.9% of NALIRIFOX patients and 6.1% of gemcitabine/nab-paclitaxel patients. Thus, these findings suggest NALIRIFOX as a first-line therapy option for patients with metastatic pancreatic cancer. 

KOL insights

“Following the potential findings of the NAPOLI 3 study, the company intends to file a supplementary new drug application; the trial's investigational regimen outperforms the standard of care, boosting median overall survival to 11.1 months' ' -Expert Opinion.


Despite so many years of research, metastatic pancreatic cancer remains one of the most notorious diseases having a high unmet need of new and effective therapies. The aggressive nature of the disease contributed to the reduced overall survival of approximately 10-15%. 

In the past few decades there have been only a handful of studies that have shown positive efficacy and safety profiles. In the NAPOLI 3 trial, the investigational regimen of ONIVYDE proved to be a superior regimen against the current standard of care treatment with nab-paclitaxel and gemcitabine, the results are quite promising, giving a ray of hope to the patients with the aggressive disease