Esophagus to Small Intestine

J Clin Oncol. 2024;42(4):410–20

Lorenzen S, Götze TO, Thuss-Patience P, Biebl M, Homann N, Schenk M, Lindig U, Heuer V, Kretzschmar A, Goekkurt E, Haag GM, Riera-Knorrenschild J, Bolling C, Hofheinz RD, Zhan T, Angermeier S, Ettrich TJ, Siebenhuener AR, Elshafei M, Bechstein WO, Gaiser T, Loose M, Sookthai D, Kopp C, Pauligk C, Al-Batran SE; AIO and SAKK Study Working Groups

Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: Interim results from the randomized, multicenter, phase 2/3 DANTE/IKF-s633 trial

Purpose: This trial evaluates the addition of the programmed death-ligand 1 (PD-L1) antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA).
Methods: DANTE started as multicenter, randomized phase 2 trial, which was subsequently converted to a phase 3 trial. Here, the authors present the results of the phase 2 proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥ cT2 or cN+) were assigned to either 4 preoperative and postoperative cycles of FLOT combined with ATZ, followed by 8 cycles of ATZ maintenance (arm A) or FLOT alone (arm B).
Results: 295 patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. 23 patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥ 1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% vs. 15% [1-sided p = 0.044]; ypT0–T2, 61% vs. 48% [1-sided p = 0.015]; ypN0, 68% vs. 54% [1-sided p = 0.012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; 1-sided p = 0.032), and the difference was more pronounced in the PD-L1 CPS ≥ 10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups.

Conclusion: Within the limitations of the exploratory nature of the data, the addition of atezolizumab to perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel is safe and improved postoperative stage and histopathologic regression.

DOI: 10.1200/jco.23.00975