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The first head-to-head trial of the two chemotherapy backbones, won narrowly by the four-drug regimen.
NAPOLI 3, trial NCT04083235 sponsored by Ipsen and reported in 2023, was the first head-to-head trial of the two chemotherapy backbones for first-line metastatic pancreatic cancer, comparing NALIRIFOX, the four-drug regimen built on liposomal irinotecan, with gemcitabine plus nab-paclitaxel. It randomised 770 patients and met its primary overall survival endpoint, with a narrow but statistically significant advantage and a clearer gain in progression-free survival, leading to FDA approval of NALIRIFOX in February 2024. OnCo links it to pancreatic ductal adenocarcinoma, to NALIRIFOX and gemcitabine plus nab-paclitaxel, to Zev A. Wainberg, and to the bottleneck of cold tumours; the result is consistent in direction with PRODIGE 4 for FOLFIRINOX. Critics note the absence of a modified FOLFIRINOX arm, so whether the new regimen beats the older four-drug standard is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
770 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survivalprimary | NALIRIFOX | 383 | 11.1 months | 0.83 (0.7 to 0.99) | 0.036 | link |
| Gemcitabine + nab-paclitaxel | 387 | 9.2 months |
This is the European standard the UK and NHS page for pancreatic cancer is compared against; NICE guideline NG85 (2018) covers the same ground with an older evidence base and a narrower set of funded drugs.
The first approved second-line regimen and the basis of NALIRIFOX, which NAPOLI 3 later moved to first line; it fixed the sequence (gemcitabine-based first, then liposomal irinotecan with fluorouracil) written into the 2018 ASCO guideline.
Shares Zev A. Wainberg, Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial, Cold tumours and the immunosuppressive microenvironment, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares MPACT, Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma.
Shares NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), FOLFIRINOX / mFOLFIRINOX, Topoisomerase-I inhibitors (and ADC payloads), Metastatic pancreatic ductal adenocarcinoma.
Shares NAPOLI-1, NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Liposomal irinotecan, Gemcitabine + nab-paclitaxel.
Shares Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, PRODIGE 4 / ACCORD 11, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma.
Shares Gemcitabine + nab-paclitaxel, FOLFIRINOX / mFOLFIRINOX, Topoisomerase-I inhibitors (and ADC payloads), Platinum agents.
Shares NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Topoisomerase-I inhibitors (and ADC payloads), Metastatic pancreatic ductal adenocarcinoma, Platinum agents.
Shares FOLFIRINOX / mFOLFIRINOX, Topoisomerase-I inhibitors (and ADC payloads), Metastatic pancreatic ductal adenocarcinoma, Platinum agents.