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129O 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

2023; Elsevier BV; Volume: 34; Linguagem: Inglês

10.1016/j.annonc.2023.10.265

1569-8041

D-Y. Oh, Yelena Y. Janjigian, S-E. Al-Batran, Zev A. Wainberg, Eric Van Cutsem, Daniela Molena, Kei Muro, Woo Jin Hyung, Lucjan Wyrwicz, Takeshi Omori, Markus Moehler, Marcelo Garrido, Sofia Oliveira, Moïshe Liberman, Victor Castro Oliden, Mehmet Bilici, John F. Kurland, Ioannis Xynos, Helen Mann, Josep Tabernero,

Colorectal Cancer Treatments and Studies

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 vs 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: 129OD + 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.