LBA77 - 5-fluorouracil and oxaliplatin with or without docetaxel in the first-line treatment of HER2 negative locally advanced (LA) unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma (GASTFOX-PRODIGE 51): A randomized phase III trial sponsored by the FFCD

Background

The perioperative FLOT triplet chemotherapy regimen is the standard of care for localized gastric and GEJ adenocarcinomas. We explored the superiority of a modified FLOT (mFLOT=TFOX regimen) vs FOLFOX in patients with advanced disease.

Methods

The GASTFOX phase III study compared FOLFOX versus a mFLOT/TFOX regimen (FOLFOX + docetaxel 50 mg/m², q2w) in the first-line setting of patients with HER2-negative, LA unresectable or metastatic gastric or GEJ adenocarcinoma, with measurable disease, an ECOG PS 0 or 1, adequate organ function, and docetaxel naïve. The primary endpoint was PFS. Secondary endpoints included OS, ORR, safety, and quality of life (QoL). For survival outcomes, HR and 95% CI were estimated by a Cox proportional hazard (PH) model. In case of non-PH, the restricted mean survival time (RMST) was used to evaluate the treatment effect.

Results

Between 12/2016 and 12/2022, 507 patients were randomized 1:1 to FOLFOX (n=253) or mFLOT/TFOX (n=254). Baseline characteristics were similar between arms (overall: male, 78%; median age, 64; PS 1, 57%; GEJ, 56%; previous (neo)adjuvant treatment, 6%). Median follow-up (F/U) was 42.8 months (mo). As compared to FOLFOX, PFS was significantly improved in patients treated with mFLOT/TFOX (median: 7.59 vs 5.98 mo, non-PH / RMST at 12 mo F/U: 7.5 vs 6.6 mo, p=0.007). OS was also significantly improved by using mFLOT/TFOX (median: 15.08 vs 12.65 mo; HR 0.82 [0.68-0.99], p=0.048). ORR was also in favor of mFLOT/TFOX (66.0 vs 56.7%, p=0.038). Most common grade ≥3 TRAE were neuropathy (31.7 vs 19.7%), diarrhea (14.5 vs 6.4%) and neutropenia (26.1 vs 18.1%) respectively for mFLOT/TFOX and FOLFOX. Median time to deterioration in QoL (> 5 points loss in EORTC QLQC30) was longer in patients treated with mFLOT/TFOX (17.0 vs 13.7 mo; HR 0.75 [0.59-0.94], p=0.015).

Conclusions

The addition of docetaxel to FOLFOX significantly improved PFS, OS and ORR in first-line treatment of advanced HER2 negative gastric or GEJ adenocarcinomas. mFLOT/TFOX can be considered as a new therapeutic option for patients eligible for a triplet regimen.

Clinical trial identification

NCT03006432.

Editorial acknowledgement

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive (FFCD).

Funding

Fédération Francophone de cancérologie Digestive (FFCD).

Disclosure

A. Zaanan: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Advisory Board: Astellas, Merck, Roche, Sanofi, Servier, Baxter, MSD, BMS, Pierre Fabre, Zymeworks, Daiichi Sankyo, AstraZeneca. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, APMONIA THERAPEUTICS, Deciphera; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. 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, Servier, MSD, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daiichi Sankyo, MSD. E. Samalin-Scalzi: Financial Interests, Personal, Advisory Board: Pierre Fabre Onoclogy, Servier FRANCE, Astellas; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Coordinating PI: Bayer; Non-Financial Interests, Member of Board of Directors: Unicancer GI, Prodige. S. Pernot: Financial Interests, Personal, Invited Speaker: Amgen, Bayer, Pierre Fabre; Financial Interests, Personal, Advisory Board: BMS, Merck, MSD, Servier. P. Artru: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche, Servier, Pierre Fabre, BMS, merck serono; Financial Interests, Personal, Invited Speaker: Amgen. F. Khemissa Akouz: Financial Interests, Personal, Invited Speaker: servier. H. Castanie: Financial Interests, Personal, Advisory Board: BMS, MSD. D. Botsen: Financial Interests, Personal, Advisory Board: Amgen, Servier, Sanofi, Pierre Fabre, Merck, Accord Healthcare. M. Muller: Financial Interests, Institutional, Invited Speaker: Servier. G. Roth: Financial Interests, Personal, Advisory Board: AstraZeneca, Accord Healthcare, AbbVie, Amgen, Bristol Myers Squibb, Ipsen, MSD, Sanofi, Servier, Viatris; Financial Interests, Personal, Other: Amgen, Bristol Myers Squibb, Ipsen, Sanofi, Lilly, Roche, AstraZeneca. T. Lecomte: Financial Interests, Personal, Invited Speaker: Ipsen, Pierre Fabre, AstraZeneca, BMS; Financial Interests, Personal, Advisory Board: SANOFI, Merck Serono, Servier, Amgen, Deciphera, Advanced Accelerator Applications, Pierre Fabre; Financial Interests, Institutional, Local PI: AstraZeneca, Mirati, ALX Oncology; Financial Interests, Institutional, Funding: Leo Pharma, Pierre Fabre. C. Lepage: Financial Interests, Personal, Advisory Board: Amgen, Advanced Accelerator Applications, Pierre Fabre, Servier. C. Louvet: Financial Interests, Personal, Advisory Board: MSD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Servier. All other authors have declared no conflicts of interest.