Analysis of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) administration in MATTERHORN: A randomized, phase 3 study of durvalumab (D) plus FLOT in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.

343 Background: In MATTERHORN (NCT04592913), D + FLOT significantly improved event-free survival (EFS) vs placebo (P) + FLOT in participants (pts) with resectable G / GEJ adenocarcinoma (Janjigian et al. N Engl J Med 2025). Dose modifications for each FLOT component could be made per local standard clinical practice. Here, we report rates of FLOT discontinuation along with EFS based on FLOT completion status. Methods: In this global, double-blind, Phase 3 study, pts with resectable G / GEJ adenocarcinoma were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT every 2 weeks on Days 1 and 15 for 4 cycles (2 cycles neoadjuvant and 2 cycles adjuvant), followed by D 1500 mg or P on Day 1 Q4W for 10 additional cycles. Rates of discontinuation of any FLOT component are reported in pts who received ≥1 dose of study treatment. EFS (time from randomization to progression, local or distant recurrence, or death) according to RECIST v1.1 per BICR and / or locally by pathology testing is reported in pts who completed all FLOT, stopped some (≥1–3 components) FLOT and stopped all FLOT. Results: Of the 944 pts who received ≥1 dose of study treatment, the proportion of pts who received all administrations of ≥1 FLOT component was similar in the D + FLOT vs P + FLOT arms in the neoadjuvant (96.0% vs 95.1%) and adjuvant (61.5% vs 64.4%) periods. The overall rate of discontinuation of ≥1 FLOT component due to adverse events (AEs) was 25.5% in the D + FLOT arm vs 20.3% in the P + FLOT arm, with higher discontinuation rates in the adjuvant (21.4% vs 15.1%) than the neoadjuvant (6.5% vs 7.7%) period (Table). The most common AEs causing FLOT discontinuation were peripheral neuropathy and neutropenia (Table). EFS was improved with D + FLOT vs P + FLOT in pts who completed all FLOT (n=228 vs 243; hazard ratio HR, 0.68; 95% confidence interval CI, 0.49–0.94), stopped some FLOT (n=63 vs 60; HR, 0.35; 95% CI, 0.16–0.71) or stopped all FLOT (n=183 vs 167; HR, 0.72; 95% CI, 0.55–0.95). Conclusions: MATTERHORN was designed for pts to receive the full perioperative FLOT regimen. In this exploratory analysis, the addition of D to FLOT did not notably impact the ability to receive FLOT; no new safety concerns were identified. EFS was improved with D + FLOT vs P + FLOT regardless of FLOT completion. Clinical trial information: NCT04592913 . Neoadjuvant Adjuvant Overall D + FLOT (n=475) P + FLOT (n=469) D + FLOT (n=365) P + FLOT (n=351) D + FLOT (n=475) P + FLOT (n=469) ≥1 FLOT component discontinuation due to AEs, n (%) 31(6.5) 36(7.7) 78(21.4) 53(15.1) 121(25.5) 95(20.3) Peripheral neuropathy* 14(2.9) 16(3.4) 7(1.9) 5(1.4) 25(5.3) 27(5.8) Neutropenia* 1(0.2) 1(0.2) 10(2.7) 7(2.0) 15(3.2) 8(1.7) Infusion-related reaction* 1(0.2) 0 12(3.3) 5(1.4) 13(2.7) 5(1.1) Hypersensitivity* 2(0.4) 1(0.2) 9(2.5) 6(1.7) 11(2.3) 7(1.5) *Occurring in ≥2% of pts in either arm overall.