LBA60 - Evaluation of gemcitabine and paclitaxel versus gemcitabine alone after FOLFIRINOX failure or intolerance in metastatic pancreatic ductal adenocarcinoma: Results of the randomized phase III PRODIGE 65 - UCGI 36 - GEMPAX UNICANCER study

Background

No clinical trial has evaluated the benefit of 2^d-line chemotherapy in metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) after FOLFIRINOX (FFX) failure.

Methods

In this randomized phase 3 trial, pts were assigned in a 2:1 ratio to either receive GEMPAX (gemcitabine 1000mg/m² + paclitaxel 80mg/m² IV infusion at D1, 8 and 15 every 28 days) (arm A/experimental) or GEM (gemcitabine alone) (arm B/control) regimen after failure or intolerance to 1^st-line FFX regimen. Primary endpoint was overall survival (OS). Secondary endpoints included Progression-Free Survival (PFS), Objective Response Rate (ORR) and safety.

Results

From June 2019 to March 2021, 211 pts were randomised (140 in arm A/71 in arm B) in 31 French centers. Median age was 64 years (30-86), 62% were male, ECOG-PS 0-1 88%. Tumor location in the pancreas was head (33%) tail (25%) or body (22%). 76% pts were metastatic at diagnosis. Median follow-up was 6.3 vs 5.9 mo in arm A vs arm B. At data cut-off, median OS (95%CI) was 6.4 (5.2-7.4) vs 5.9 mo (4.6-6.9) in arm A vs arm B (HR=0.87 [0.63-1.20]; p=0.4095), median PFS 3.1 (2.2-4.3) vs 2.0 mo (1.9-2.3) (HR=0.64 [0.47-0.89]; p=0.0067), and ORR 19% (13-27) vs 5% (1-13%) (p=0.008). Overall, 17% pts in arm A and 3% in arm B discontinued their treatment due to treatment-related adverse events (TRAEs). Grade (G) 3/4 TRAEs were reported in 58% vs 27% in arm A vs arm B among which 15% vs 4% anaemia, 16% vs 16% neutropenia, 20% vs 4% thrombocytopenia, 10% vs 3% asthenia and 12% vs 0% neuropathy. Only one G 5 TRAE was reported in arm A (acute respiratory distress). Noticeably, 32% (arm A) vs 47% (arm B) pts received 3^rd-line therapy including taxanes (2% vs 23%), platinum salts (9% vs 10%) or irinotecan (9% vs 1%).

Conclusions

The combination of paclitaxel + gem brought no benefit in OS over gem alone to mPDAC pts in 2^nd-line setting but significantly improved both PFS and ORR. Imbalance in 3^rd line therapies and notably the use of taxanes in gem monotherapy arm might explain the lack of benefit in OS. Altogether, these results highlight the medical need for new therapeutic options for pre-treated mPDAC pts.

Clinical trial identification

NCT03943667 EudraCT: 2018-002886-21.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

INCa (Institut National du Cancer).

Disclosure

C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol-Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai; Financial Interests, Institutional, Invited Speaker: Pierre Fabre Oncologie, Servier. D. Malka: Financial Interests, Personal, Expert Testimony: AbbVie; Financial Interests, Personal, Advisory Board: Agios, Amgen, AstraZeneca, BMS, Bayer, HalioDx, Incyte, MSD, Merck Serono, Pierre Fabre Oncologie, Roche, Servier, Taiho; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Bayer, Foundation Medicine, HalioDx, Incyte, Leo Pharma, MSD, Medscape, Merck Serono, Pierre Fabre Oncologie, Roche, Sanofi, Servier, Viatris, Veracyte; Other, Other, Travel expenses for medical congresses: Amgen, Bayer, BMS, Merck Serono, Pierre Fabre Oncologie, Roche, Sanofi, Servier, Viatris. J. Raimbourg: Financial Interests, Personal, Invited Speaker, Travel reimbursement: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, Amgen, Sanofi; Financial Interests, Personal, Other, invited speaker and travel reimbursement: Pierre Fabre. D. Botsen: Non-Financial Interests, Personal, Other, non-financial support: GSK, Novartis, Roche, Servier, Amgen; Financial Interests, Personal, Other, personal fees: Pierre Fabre; Financial Interests, Personal, Invited Speaker, personal fees: Chugai. M. Jary: Financial Interests, Personal, Invited Speaker: pierre fabre, servier, incyte; Other, Other, participation to congresses: pierre fabre; Other, Other, Participation to congresses: roche, bayer. J. Bachet: Financial Interests, Personal, Other, honoraria and consulting: AMGEN, MSD, Pierre Fabre, Servier; Financial Interests, Personal, Other, honoraria, consulting and research grant: AstraZeneca; Financial Interests, Personal, Other, honoraria, consulting and travel reimbursement: Bayer, Merck Serono; Financial Interests, Personal, Other, honoraria and travel reimbursement: Roche, Sanofi; Financial Interests, Personal, Other, honoraria: VIATRIS; Financial Interests, Personal, Advisory Role: Incyte. C. Neuzillet: Financial Interests, Personal, Advisory Role: Servier, Amgen, Novartis, Incyte, Nutricia, Baxter; Financial Interests, Personal, Other, consulting, principal investigator: AstraZeneca, BMS; Financial Interests, Personal, Other, consulting, congresses reimbursement: Merck, MSD, Mylan; Financial Interests, Personal, Other, congresses reimbursement, principal investigator: Ose Immunotherapeutics; Financial Interests, Personal and Institutional, Other, congresses reimbursement and funding (institutional): Roche. N. Williet: Financial Interests, Personal, Advisory Role: Accord Healthcare, Mayoly, Viatris; Financial Interests, Personal, Other, consulting and travel reimbursement: Servier; Financial Interests, Personal, Other, travel reimbursement: Ipsen, MSD. O. Bouche: Financial Interests, Personal, Other, honoraria: Amgen, Apmonia Therapeutics, Bayer, Merck, Pierre Fabre, Roche, Sanofi, Servier. F. Ghiringhelli: Financial Interests, Personal and Institutional, Other, honoraria, consulting, research grant (institutional), travel reimbursement: Roche; Financial Interests, Personal, Other, honoraria, research grant (institutional), travel reimbursement: AstraZeneca; Financial Interests, Personal, Other, honoraria: Merck Serono, BMS, MSD, Bayer; Financial Interests, Personal, Other, honoraria and travel reimbursement: Amgen; Financial Interests, Personal, Invited Speaker, honoraria and travel reimbursement: Servier. All other authors have declared no conflicts of interest.