Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial

TY - JOUR

T1 - Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial

AU - Lorenzen, Sylvie

AU - Götze, Thorsten Oliver

AU - Thuss-Patience, Peter

AU - Biebl, Matthias

AU - Homann, Nils

AU - Schenk, Michael

AU - Lindig, Udo

AU - Heuer, Vera

AU - Kretzschmar, Albrecht

AU - Goekkurt, Eray

AU - Haag, Georg Martin

AU - Riera-Knorrenschild, Jorge

AU - Bolling, Claus

AU - Hofheinz, Ralf-Dieter

AU - Zhan, Tianzuo

AU - Angermeier, Stefan

AU - Ettrich, Thomas Jens

AU - Siebenhuener, Alexander Reinhard

AU - Elshafei, Moustafa

AU - Bechstein, Wolf Otto

AU - Gaiser, Timo

AU - Loose, Maria

AU - Sookthai, Disorn

AU - Kopp, Christina

AU - Pauligk, Claudia

AU - Al-Batran, Salah-Eddin

AU - AIO and SAKK Study Working Groups

PY - 2024/2/1

Y1 - 2024/2/1

N2 - PURPOSE: This trial evaluates the addition of the 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 II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B).RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three 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% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .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 ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.

AB - PURPOSE: This trial evaluates the addition of the 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 II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B).RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three 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% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .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 ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.

KW - Humans

KW - Fluorouracil/adverse effects

KW - Docetaxel/therapeutic use

KW - Oxaliplatin/therapeutic use

KW - Leucovorin/adverse effects

KW - B7-H1 Antigen/therapeutic use

KW - Stomach Neoplasms/drug therapy

KW - Esophageal Neoplasms/drug therapy

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Adenocarcinoma/drug therapy

KW - Esophagogastric Junction/pathology

KW - Neoadjuvant Therapy/methods

KW - Antibodies, Monoclonal, Humanized

U2 - 10.1200/JCO.23.00975

DO - 10.1200/JCO.23.00975

M3 - SCORING: Journal article

C2 - 37963317

VL - 42

SP - 410

EP - 420

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 4

ER -