First Line Metastatic Pancreatic Cancer : 5FU/LV+Nal-IRI, Gemcitabine+Nab-paclitaxel or a Sequential Regimen of 2 Months 5FU/LV+Nal-IRI

Summary

In Europe, pancreatic cancer (PC) is the 7th most common cancer and the 5th leading cause of cancer death in Europe. Each year, the number of deaths due to prostate cancer is almost as high as the number of new cases diagnosed reflecting the poor prognosis associated with this disease. PC is insidious and is often diagnosed late. Despite advances in the management of other more common gastrointestinal cancers, the treatment of PC has had few benefits inherent in recent advances in digestive oncology. Gemcitabine has thus remained the reference treatment for more than 10 years. Recent studies have shown that gemcitabine/Nab-paclitaxel combination therapy is more effective in PC than gemcitabine-based therapy alone. In addition, multidrug therapy approaches (Irinotecan-5FU/LV) have also emerged to avoid the emergence of resistance to treatments while limiting toxicities. The recently developed Nal-IRI has also shown interesting efficacy in patients with metastatic PC previously treated with gemcitabine, with improved overall survival median and limited toxicity. Based on this information, the NAPOLI trial was conducted in patients with second line PC comparing the efficacy of Nal-IRI/5FU/LV or Nal-IRI and 5FU/LV alone; in this key study, the combination Nal-IRI/5FU/LV treatment was more effective than monotherapies (Nal-IRI or 5FU/LV alone). Based on all these data, a Phase II trial testing the standard of care gemcitabine/nab-paclitaxel vs Nal-IRI/5FU/LV vs Nal-IRI/5FU/LV 2-months sequential regimen followed by gemcitabine/nab-paclitaxel will be performed. This will allow us to i) know the tolerance and efficacy of Nal-IRI/5FU/LV in the first line of treatment, ii) test a new sequential strategy with Nal-IRI but also iii) compare our results in the experimental arms with one of the two world standard therapeutic regimens: gemcitabine + nab-Paclitaxel. All this in order to improve the management of patients with PC from the first line of treatment.

Timeline

Start

2018-11-16

Primary completion

2025-01-10

Completion

2025-01-10

Outcome

Missed primary endpoint

paper Neither sequential (HR = 0.76, p = 0.072) nor NAPOLI regimens (HR = 1.20, p = 0.22) lead to a statistically significant improvement of PFS over the MPACT regimen. PMID 42256682 ↗

Publications

• Taieb J, Pernot S, Thuillier F, Delattre A, Vo-Quang E, Petorin C, Bourgeois V, Tougeron D, Audemar F, Vitellius C, Mosser L, Desrame J, Di Fiore F, Rinaldi Y, Pellat A, Bolliet M, Watelle F, Perrier H, Dubreuil O, Lepage C, Bachet JB. Sequential alternation of nal-IRI/5-FU and gemcitabine/nab-paclitaxel versus nal-IRI/5-FU versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic cancer: results of the randomized phase II PRODIGE 61-FUNGEMAX trial (France). EClinicalMedicine. 2026 May 29;96:103998. doi: 10.1016/j.eclinm.2026.103998. eCollection 2026 Jun.

Drugs

Indications