KEY TAKEAWAYS
- The phase III NAPOLI 3 trial compared NALIRIFOX’s effectiveness and safety against nab-paclitaxel + gemcitabine as an initial treatment for mPDAC.
- The study’s main endpoint was OS, with secondary outcomes including PFS and ORR.
- As a first-line treatment, NALIRIFOX notably improved OS and PFS over Gem+NabP for mPDAC patients.
In the NAPOLI 3 trial, patients (pts) diagnosed with untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) were evenly distributed to receive either the liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) or gemcitabine + nab-paclitaxel (Gem+NabP) treatments during 28-day cycles. The main outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS) and overall response rate (ORR) based on standardized tumor response criteria.
In total, 770 participants were part of the study, with 383 receiving NALIRIFOX and 387 getting Gem+NabP. Both groups had comparable baseline traits. After an average monitoring period of 16.1 months, there were 544 notable events. The NALIRIFOX group had an average overall survival (OS) of 11.1 months, while the Gem+NabP group’s OS was 9.2 months. By the 18-month mark, 26.2% of the NALIRIFOX group were still alive compared to 19.3% in the Gem+NabP group. The average duration before disease progression, or progression-free survival (PFS), was 7.4 months for NALIRIFOX and 5.6 months for Gem+NabP.
At 18 months, 11.4% of NALIRIFOX and 3.6% of Gem+NabP recipients hadn’t shown disease progression. Excluding data after starting another cancer treatment, NALIRIFOX pts had an OS of 15.1 months versus 9.2 months in the Gem+NabP group. The overall response rate (ORR) was 41.8% for NALIRIFOX and 36.2% for Gem+NabP, with the median response duration being 7.3 and 5.0 months, respectively. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported as follows: the NALIRIFOX group (n=370) saw higher rates of diarrhea (20.3%), nausea (11.9%), and low potassium levels (15.1%). In contrast, the Gem+NabP group (n=379) showed higher frequencies of anemia (17.4%) and a decrease in white blood cells or neutropenia (24.5%).
The study demonstrated that using NALIRIFOX as the initial treatment showed a significant increase in OS and PFS compared to Gem+NabP in mPDAC pts. The side effects of NALIRIFOX were in line with its components and were generally manageable. These findings highlighted NALIRIFOX as a potential primary treatment choice for mPDAC pts.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00158-8/fulltext
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04083235
Wainberg, Z., Melisi, D., Macarulla, T., Cid, R.P., Chandana, S., Fouchardière, C.D.L., Dean, A., Kiss, I., Lee, W., Goetze, T., Cutsem, E.V., Paulson, S., Bekaii-Saab, T., Pant, S., Hubner, R., Xiao, Z., Chen, H., Benzaghou, F., O’Reilly, E. O-1 Liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma: Sensitivity analysis of survival from the NAPOLI 3 trial. https://doi.org/10.1016/j.annonc.2023.04.016
