LBA57 - Unicancer PRODIGE 24/CCTG PA6 trial: Updated results of a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX (mFFX) versus gemcitabine (gem) in patients (pts) with resected pancreatic ductal adenocarcinomas (PDAC)

Background

mFFX combination was shown to be superior to Gem alone in adjuvant setting after resection of PDAC for DFS and OS, after a median follow-up (fu) of 36 months (mo) but data were immature, 61% of pts being alive (Conroy T et al., NEJM 2018). Thus, prognostic factors (PrF) for OS were not determined.

Methods

Pts aged 18-79 years (yr) with histologically proven PDAC, WHO PS ≤1, no cardiac ischemia were eligible. Randomization was stratified by center, pN, R margin status and post-operative CA 19-9 level (≤90 vs >90 U/mL). Pts received mFOLFIRINOX every 14 days for 12 cycles or Gem 1000 mg/m² on days 1, 8, and 15 for six 28-day cycles. Primary endpoint was DFS. Secondary endpoints were OS, metastasis-free survival (MFS), specific survival (SS) and safety. 490 pts (for 342 events) were needed to detect a 10% difference in 3-yr DFS with 80% power (log-rank test with 5% 2-sided α). HR and 95% CI were estimated by a stratified Cox proportional hazard model. Here, we present updated 5-yr outcomes and PrF for OS in the intent-to-treat population.

Results

493 patients had been included and followed, including those alive ≥ 5 yr. With a median fu of 69.7 mo (95% CI: 67.0-73.9), 367 DFS events were observed and the 5-yr DFS rate was 26.1% (95% CI: 20.5-32.1) with mFFX vs 19.0% (95% CI: 14.3-24.3) with Gem, stratified HR=0.66 (95% CI: 0.54-0.82), p=0.0001. The median OS was 53.5 mo (95% CI: 43.5-58.4) in mFFX arm vs 35.5 mo (95% CI: 30.1-40.3) in Gem arm, stratified HR=0.68 (95% CI: 0.54-0.85), p=0.0009. The 5-yr OS rate is 43.2% (95% CI: 36.5-49.7) in mFFX arm vs 31.4% (95% CI 25.5-37.5) in Gem arm. MFS was 29.4 mo (95% CI: 21.4-40.1) in mFFX arm vs 17.7 (95% CI: 14.0-21.2) in Gem arm, stratified HR=0.64, (95% CI: 0.52-0.80), p=0.0001. Median SS was 54.7 mo [45.8-68.4] in mFFX arm vs 36.3 mo [30.5-43.9] in Gem arm, stratified HR=0.65, (95% CI: 0.51-0.82), p=0.0003. Treatment arm, center volume of inclusions, tumor grade, tumor staging, and age were significant PrF for OS in multivariate analysis.

Conclusions

With ≥5 yr fu, updated results of PRODIGE 24/CCTG PA6 trial confirm that adjuvant FFX yields significantly longer DFS, OS, MFS and SS compared to Gem.

Clinical trial identification

EudraCT 2011-002026-52; NCT01526135.

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

Unicancer; INCA; Ligue Nationale Contre le Cancer.

Disclosure

P. Hammel: Financial Interests, Institutional, Other, Financial support for study outside the submitted work: Astrazeneca; Financial Interests, Personal, Other, Personal Fees outside the submitted work: BMS; Financial Interests, Institutional, Other, Financial support for study outside the submitted work: Erytech; Financial Interests, Personal, Other, Personal Fees outside the submitted work: Servier; Financial Interests, Personal, Other, Personal Fees outside the submitted work: Mylan; Financial Interests, Institutional, Other, Financial support for study outside the submitted work: Halozyme. A. Turpin: Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Expert Testimony: Merck-Serono; Financial Interests, Personal, Expert Testimony: Mylan; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: AstraZeneca. A. Wei: Financial Interests, Personal, Other, Consulting outside of the submitted work: AstraZeneca; Financial Interests, Personal, Other, Consulting outside of the submitted work: Histosonics; Financial Interests, Personal, Other, Travelling costs outside of the submitted work: Intuitive Surgical. A. Lopez: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Other, Lecture fees: Vifor pharma; Financial Interests, Personal, Other, Lecture fees: Bayer; Financial Interests, Personal, Other, Lecture fees: Merck; Financial Interests, Personal, Other, Lecture fees: Sanofi; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): AbbVie; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): Amgen; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): MSD; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): Vifor-Pharma; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): Mundi Pharma; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): Ipsen; Financial Interests, Personal, Other, Travel accomodation expenses (not for this work): Novartis; Financial Interests, Personal, Other, Consultant: Amgen. E. Francois: Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Sponsor/Funding: Amgen; Financial Interests, Personal, Advisory Role: MSD. P. Artru: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Bayer. T. Lecomte: Financial Interests, Institutional, Principal Investigator: Ipsen; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: ERYTHEC Pharma; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Role: Ipsen. E. Assenat: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Bayer. O. Bouche: Financial Interests, Personal, Other, Honoraria (self): Merck KGaA; Financial Interests, Personal, Other, Honoraria (self): Roche; Financial Interests, Personal, Other, Honoraria (self): Bayer; Financial Interests, Personal, Other, Honoraria (self): AstraZeneca; Financial Interests, Personal, Other, Honoraria (self): Grunenthal; Financial Interests, Personal, Other, Honoraria (self): MSD; Financial Interests, Personal, Other, Honoraria (self): Amgen; Financial Interests, Personal, Other, Honoraria (self): Servier; Financial Interests, Personal, Other, Honoraria (self): Pierre Fabre; Financial Interests, Personal, Advisory Role: Merck KGaA; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Grunenthal; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, Speaker Bureau/Expert Testimony: Amgen; Financial Interests, Personal, Other, Speaker Bureau/Expert Testimony: Servier; Financial Interests, Personal, Other, Speaker Bureau/Expert Testimony: Pierre Fabre; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Servier. A. Lambert: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Viatris; Financial Interests, Personal, Advisory Board: Roche; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: Innovent Biologics; Non-Financial Interests, Personal, Principal Investigator: Keocyt; Non-Financial Interests, Personal, Principal Investigator: MSD. P. Rat: Financial Interests, Personal, Royalties: HIPEC device – Landanger society, Chaumont, France; Non-Financial Interests, Personal, Member: AFC - Société de Chirurgie de Lyon. J. Bachet: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Servier. All other authors have declared no conflicts of interest.