1296MO - PRODIGE 29-UCGI 26(NEOPAN): A phase III randomised trial comparing chemotherapy with folfirinox or gemcitabine in locally advanced pancreatic carcinoma (LAPC)

Background

Pancreatic carcinoma (PC) is an aggressive malignancy and the 4th cause of all cancer deaths worldwide. More than 30% of patients with PC are unresectable because of the local extension with a median overall survival (OS) of less than one year. Folfirinox (FFX) is superior to gemcitabine in the treatment of metastatic PC, in terms of OS and progression-free survival (PFS) but standard of care remains gemcitabine (gem) for LAPC.

Methods

Pts with histologically proven LAPC not suitable for surgery, WHO PS ≤1, no cardiac ischemia were eligible. Randomization was stratified by center, tumour localization (pancreas head yes/no), WHO PS (0 vs 1) and age (≤60yr vs > 60yr). Pts received FFX (every 14 days for 12 cycles) or Gem 1000 mg/m² on days 1, 8, and 15 for six 28-day cycles excepted for cycle 1 with an infusion at D22. Primary endpoint was PFS. Secondary endpoints were OS, percentage of secondary curative-intent surgery, objective response rate, disease control rate, time to treatment failure, quality of life and safety. A total of 170 pts (142 events) were needed to detect an increase of 3 months (mo) in PFS with 80% power (log-rank test, 5% 2-sided α). HR and 95% CI will be estimated by a stratified Cox proportional hazard model. PFS and OS outcomes will be presented in the intent-to-treat population.

Results

A total of 171 patients aged 35-84 years (yr) were included and followed for a maximum of 5 yr. With a median follow-up of 43.7 mo, 146 PFS events were observed and the median PFS was 9.8 mo (95% CI: 7.2; 11.7) with FFX vs 7.5 mo% (95% CI: 6.0 ; 9.2) with Gem, stratified HR=0,57 (95% CI: 0.3 ; 1.08), p=.0468. The median OS was 15.1 mo (95% CI: 11.9 ; 20.3) in FFX arm vs 15.6 mo (95% CI:11.7 ; 18.6) in Gem arm, stratified HR=1.03 (95% CI: 0.53 ; 1.98), p=0.66. FFX treatment was well tolerated. AEs of grade ≥ 3 were reported in 32 patients (38%) in Arm Gem and 35 in arm FFX (41%).

Conclusions

PRODIGE 29/NEOPAN trial results shows that FFX yields significantly longer PFS compared to Gem and was well tolerated. No significant difference in OS was observed between both groups. Other secondary endpoints are currently explored, and will be presented during ESMO meeting.

Clinical trial identification

NCT02539537.

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

Institut National du Cancer (INCA).

Disclosure

M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck Kga, Pfizer, Bayer, Lilly; Financial Interests, Personal, Advisory Board: Roche, Basilea, Sotio, Pierre Fabre, Bohringer, Rafael, Servier, Zymeworks, Ipsen, Bayer, Glaxo Smith Kline, HalioDX, Lilly; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of bevacizumab in NET: Roche; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of steptozotocin in NET: Keocyt; Financial Interests, Institutional, Invited Speaker: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; My wife is head of the oncology business unit in the French Affiliate of Sandoz: Sandoz France. F. Di Fiore: Financial Interests, Personal, Invited Speaker, Honoraria/Travel/Accomodation/Expenses: Roche, Amgen, Merck, Sanofi, Ipsen, Servier, Pierre Fabre; Financial Interests, Personal, Invited Speaker, Honoraria: Bayer, Novartis, Jenssen, Mylan, MSD, bms. P. Follana: Financial Interests, Personal, Invited Speaker: GSK, Eisai, MSD; Financial Interests, Personal, Expert Testimony: Clovis, Novartis; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Other, Congress invitation: GILEAD. J. Bachet: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Merck Serono, MSD, Pierre Fabre, Roche; Financial Interests, Personal, Other, Honoraria: Sanofi, Servier; Financial Interests, Personal, Invited Speaker: Viatris; Non-Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Funding: AstraZeneca. T. Lecomte: Financial Interests, Personal, Other, Honoraria: Sanofi, Merck, Servier, Amgen, Ipsen, Pierre Fabre, AstraZeneca, Deciphera, Bayer. F. El Hajbi: Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Servier, Merck, AAA. V. Ly Lebrun: Financial Interests, Personal, Other, Honoraria: IPSSEN. O. Bouche: Financial Interests, Personal, Other, Honoraria: Amgen, Apmonia, Therapeutics, Bayer, Merck, Pierre Fabre, Roche, Sanofi, Servier. All other authors have declared no conflicts of interest.