Surgical journey for participants (pts) in the MATTERHORN trial: A global, randomized, phase 3 study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.

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353 Background: In MATTERHORN (NCT04592913), perioperative D + FLOT significantly improved event-free survival (EFS) vs placebo (P) + FLOT in pts with resectable G/GEJ adenocarcinoma (Janjigian et al. N Engl J Med 2025). The surgical journey for pts in MATTERHORN is described. Methods: In this global, Phase 3, double-blind study, pts with resectable G/GEJ adenocarcinoma were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W; Day 1 of each cycle) + FLOT Q2W (Days 1 and 15 of each cycle) for 4 cycles (2 cycles each neoadjuvant / adjuvant), followed by D 1500 mg or P Q4W for 10 cycles. Surgery delays, adjuvant treatment (tx) initiation delays and EFS by surgical status were assessed in the full analysis set (randomized pts; FAS); surgical morbidities and mortalities were assessed in the safety analysis set (pts with ≥1 tx dose; SAS). Results: Of 948 pts randomized to D + FLOT (n=474) or P + FLOT (n=474), 90.9% vs 90.3% attempted surgery, 10.1% vs 10.8% had a surgery delay, and 86.9% vs 84.4% completed surgery. The most common surgery delay was <2 weeks for pts in the D + FLOT (5.9%) and P + FLOT (5.9%) arms. In the D + FLOT vs P + FLOT arms, 2.3% vs 4.6% of pts had an adjuvant tx initiation delay. Median (range) time from surgery to adjuvant tx initiation was 56 (29–152) vs 56 (31–186) days. Among pts in the SAS (D + FLOT [n=475] vs P + FLOT [n=469]), serious adverse events possibly related to surgery were 12.8% vs 13.0%. Of pts in the SAS who completed surgery (D + FLOT [n=413] vs P + FLOT [n=399]), mortality rates were 1.2% vs 1.5% within 30 days of surgery and 3.1% vs 2.0% within 90 days of surgery. Of pts in the FAS who completed surgery (D + FLOT [n=412] vs P + FLOT [n=400]), 91.5% vs 92.3% had an R0 resection, 5.6% vs 5.3% had an R1 resection, and 2.7% vs 2.5% had an R2 resection; 91.0% vs 93.3% had a D2 / D3 lymphadenectomy. Among pts randomized to D + FLOT vs P + FLOT, 35.4% vs 35.0% had a total gastrectomy and 26.8% vs 26.2% had a gastroesophagectomy. D + FLOT improved EFS vs P + FLOT in pts who completed surgery, regardless of tumor location, resection margin or type of lymphadenectomy (Table). Conclusions: In pts with resectable G / GEJ adenocarcinoma, the surgical journey did not differ with D + FLOT vs P + FLOT. EFS benefit with D + FLOT was observed irrespective of tumor location, resection margin or lymphadenectomy type. Clinical trial information: NCT04592913 . D + FLOT n P + FLOT n EFS hazard ratio vs P + FLOT(95% CI) Tumor location G 276 265 0.70 (0.52–0.94) GEJ 136 135 0.64 (0.43–0.95) Resection margin R0 377 369 0.67 (0.51–0.86) R1 23 21 0.58 (0.28–1.19) Type of lymphadenectomy D1 36 26 0.75 (0.33–1.70) D2 / D3 375 373 0.67 (0.52–0.86)