Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study

The global, Phase 3, randomised, double-blind, placebo (P)-controlled MATTERHORN study (NCT04592913) assesses perioperative durvalumab (D) with FLOT in participants (pts) with resectable GC/GEJC. Results of a pre-planned interim analysis (IA) are reported. Pts with resectable (>T2 N0-3 M0/T0-4 N1-3 M0) GC/GEJC were randomised 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT Q2W on Days 1 and 15 for 4 cycles (2 doses of D or P and 4 doses of FLOT pre- and post-operative), followed by D 1500 mg or P on Day 1 Q4W for 10 further cycles. IA was conducted after all randomised pts underwent or were precluded from surgery. Superiority of pCR rate (α=0.1% [2-sided]) by central review (Modified Ryan) was assessed. Surgical and safety outcomes were also assessed. There were 474 pts randomised to each treatment arm. Baseline characteristics were balanced between arms; 19% of pts in each enrolled in Asia. The majority of pts had GC (68%), cT3 (66%; cT4, 25%) and cLN+ (70%). A statistically significant improvement in pCR was observed with addition of D to FLOT versus P (19% vs 7%; Δ12%; odds ratio [OR], 3.08; p<0.00001; Table). Combined pCR/near-complete pathological response (pnCR) rate was 27% with D vs 14% with P. Surgery rate and R0 resection rate (in pts who underwent surgery) were similar with D (87% and 86%, respectively) vs P (84% and 86%, respectively). Downstaging favoured D vs P (pT0, 21% vs 10%; pN0, 47% vs 33%; by central review). Median D and P exposure was similar. Adverse event rates were similar between arms (Table).Table: LBA73D + FLOT (n=474)P + FLOT (n=474)pCRn; % (95% CI)91; 19 (15.8–23.0)34; 7 (5.0–9.9)OR (95% CI)3.08 (2.03–4.67); p<0.00001pCR/pnCRn; % (95% CI)127; 27 (22.9–31.0)68; 14 (11.3–17.8)OR (95% CI)2.19 (1.58–3.04); p<0.00001Surgery performedn; % (95% CI)411; 87 (83.3–89.6)399; 84 (80.6–87.4)OR (95% CI)1.23 (0.85–1.76)R0 resection*n; % (95% CI)369; 86 (82.2–89.0)362; 86 (82.1–89.0)OR (95% CI)1.00 (0.68–1.48)AE†, n (%)470 (99)463 (99)Grade 3/4326 (69)317 (68)TRAE452 (95)441 (94)Grade 3/4 TRAE275 (58)264 (56)*In pts with surgery: D + FLOT, n=430, P + FLOT, n=422. †In safety analysis set: D + FLOT, n=475, P + FLOT, n=469. TRAE, treatment-related AE. Open table in a new tab *In pts with surgery: D + FLOT, n=430, P + FLOT, n=422. †In safety analysis set: D + FLOT, n=475, P + FLOT, n=469. TRAE, treatment-related AE. The addition of D to perioperative FLOT therapy demonstrated a clinically meaningful and statistically significant improvement in pCR in resectable GC/GEJC, with a tolerable safety profile. The MATTERHORN study is ongoing for the primary endpoint of event-free survival.