Durvalumab (PD-L1 blockade) + perioperative FLOT boosts EFS across completion strata in resectable G/GEJ cancer (MATTERHORN)

Durvalumab (anti–PD-L1 monoclonal antibody) was added to perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) in MATTERHORN, a global, double-blind Phase 3 trial in untreated, resectable gastric/gastroesophageal junction adenocarcinoma (NCT04592913). In this treatment-period analysis, EFS favored durvalumab + FLOT vs placebo + FLOT regardless of which perioperative components were started/completed, with the strongest outcomes in patients completing all adjuvant immunotherapy (completed all adjuvant D/Pbo: 24-mo EFS 91.8% vs 87.2%; HR 0.63 [95% CI 0.41–0.97]; received any adjuvant but did not complete D/Pbo: 24-mo EFS 46.7% vs 29.8%; HR 0.65 [0.46–0.91]; neoadjuvant + surgery but no adjuvant: 24-mo EFS 49.2% vs 33.3%; HR 0.65 [0.38–1.13]; neoadjuvant started but no surgery: 24-mo EFS 10.0% vs 6.2%; HR 0.80 [0.55–1.18]) (subgroup/landmark readouts; interpret cautiously). Safety burden was largely chemotherapy-driven overall (Grade 3–4 AEs 71.6% vs 71.2%; SAEs 48.2% vs 44.1%), while the adjuvant monotherapy period was markedly lower in both arms (Grade 3–4 AEs 21.2% vs 20.5%; SAEs 14.5% vs 14.5%), with discontinuations of durvalumab/placebo in adjuvant monotherapy at 5.8% vs 2.7%—a modest added drop-off that looks within the expected range for PD-(L)1 maintenance in curative-intent settings.