1520P - Perioperative treatment in resectable gastric cancer with spartalizumab combined with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT): The GASPAR phase II trial

Background

Perioperative chemotherapy with FLOT is a standard of care for patients (pts) with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma, despite a still poor prognosis. This trial evaluates the anti–PD-1 antibody spartalizumab combined to FLOT as perioperative treatment (tt) for resectable pts.

Methods

GASPAR trial is a multicenter, single arm, phase II trial. Pts with untreated localized gastric or GEJ adenocarcinoma considered resectable (≥ cT2 or cN+) were enrolled. Pts received 4 pre- and post-operative cycles of FLOT (Docetaxel 50 mg/m², oxaliplatine 85 mg/m², leucovorin 200 mg/m² and fluorouracile 2600 mg/m² 24h infusion, q2w) and 2 pre- and post-operative cycles of spartalizumab (fixed dose of 400 mg, q4w). The main endpoint was the rate of pathological complete regression (pCR) assessed using Becker criteria.

Results

In total, 68 pts were included: men (78%), median age 63 yrs [range 31-79], cT3/T4 51%, GEJ 60%, cN+ 18/48 pts. Among 67 pts who started the tt, 64 (96%) received 2 pre-operative cycles of spartalizumab, the 3 others received 1 cycle due to toxicity. Similarly, 64 (96%) pts completed the 4 pre-cycles of FLOT, 1 discontinued after 2 cycles (toxicity), the 2 others received 3 cycles (pt decision). FLOT administration was delayed for 13 pts (19%) due to toxicity, and 26 pts (39%) observed dose reduction. Surgery, performed in 65 pts (97%) within 38 days from the end of pre-operative tt in median [range 23-67], was R0 for 62 pts (95%). Among 64 pts assessable for efficacy, pCR was observed for 20 pts (31%), and sub-total regression (<10% residual tumor) for 12 pts (19%), meaning a major response rate of 50%. After a median follow-up of 6.9 months, 8 pts are still under adjuvant tt. No toxic death, nor spartalizumab-related grade (G) 4 adverse events (AEs) were observed. 5 pts developed G3 immune-mediated AEs: pancreatitis (2), hepatitis, enterocolitis and encephalitis. 15 pts (23%) experienced post-surgery G3/4 complications.

Conclusions

Spartalizumab combined with FLOT shows high efficacy as perioperative tt in pts with resectable gastric or GEJ adenocarcinoma with a high rate of pathological complete regression and an acceptable safety profile.

Clinical trial identification

NCT04736485.

Editorial acknowledgement

Legal entity responsible for the study

Comprehensive Cancer centre Francois Baclesse, Caen, France.

Funding

French Cancer Institute and the French Fondation ARC (Ref INCa-ARC_14842) Spartalizumab provided free of charge to enrolled patients by Novartis.

Disclosure

G. Piessen: Other, Personal, Advisory Role: Bristol Myers Squibb, Nestle health science, MSD Oncology, Astellas Pharma. R. Guimbaud: Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Advisory Role: BMS, MSD, Pierre Fabre, Servier; Financial Interests, Personal, Other, Travel, accommodations, expenses: Servier, Pierre Fabre, Ipsen, MSD. S. Pernot: Financial Interests, Personal, Other, Honoraria: MSD Oncology, Servier, BMS GmbH & Co. KG, Amgen, AstraZeneca; Financial Interests, Personal, Other, Honoraria, Travel, accommodations, expenses: Pierre Fabre; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Servier, Pierre Fabre. S.M. Le Sourd: Financial Interests, Personal, Advisory Role, Honoraria: Servier, Pierre Fabre, AstraZeneca. E. Samalin-Scalzi: Financial Interests, Personal, Advisory Role, Honoraria: Pierre Fabre Oncology; Financial Interests, Personal, Advisory Role, Consulting: Amgen Servier, Pierre Fabre Oncology, MSD, BMS; Financial Interests, Institutional, Research Funding: Bayer; Financial Interests, Personal, Other, Travel, accommodations, expenses: Servier, Pierre Fabre Oncology, MSD, Merck. All other authors have declared no conflicts of interest.