Surgical and pathological outcome, and pathological regression, in patients receiving perioperative atezolizumab in combination with FLOT chemotherapy versus FLOT alone for resectable esophagogastric adenocarcinoma: Interim results from DANTE, a randomized, multicenter, phase IIb trial of the FLOT-AIO German Gastric Cancer Group and Swiss SAKK.

person Salah-Eddin Al-Batran Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt Am Main, Germany and Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt Am Main, Germany info_outline Salah-Eddin Al-Batran, Sylvie Lorenzen, Peter C. Thuss-Patience, Nils Homann, Michael Schenk, Udo Lindig, Vera Heuer, Albrecht Kretzschmar, Eray Goekkurt, Georg Martin Haag, Jorge Riera Knorrenschild, Claus Bolling, Ralf-Dieter Hofheinz, Stefan Angermeier, Thomas Jens Ettrich, Alexander Siebenhuener, Christina Kopp, Claudia Pauligk, Thorsten Oliver Goetze, Timo Gaiser

Authors person Salah-Eddin Al-Batran Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt Am Main, Germany and Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt Am Main, Germany info_outline Salah-Eddin Al-Batran, Sylvie Lorenzen, Peter C. Thuss-Patience, Nils Homann, Michael Schenk, Udo Lindig, Vera Heuer, Albrecht Kretzschmar, Eray Goekkurt, Georg Martin Haag, Jorge Riera Knorrenschild, Claus Bolling, Ralf-Dieter Hofheinz, Stefan Angermeier, Thomas Jens Ettrich, Alexander Siebenhuener, Christina Kopp, Claudia Pauligk, Thorsten Oliver Goetze, Timo Gaiser Organizations Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt Am Main, Germany and Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt Am Main, Germany, Klinikum rechts der Isar, Technische Universität München, Klinik für Innere Medizin III, Munich, Germany, Charité–Universitätsmedizin Berlin, Med. Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany, Klinikum Wolfsburg, Med. Klinik II, Wolfsburg, Germany, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany, Universitätsklinikum Jena, Klinik für Innere Medizin II (Hämatologie/Onkologie), Jena, Germany, MVZ St. Anna Hospital Herne, Herne, Germany, MVZ Mitte, Onkologische Schwerpunktpraxis Leipzig, Leipzig, Germany, Hämatologisch-Onkologische Praxis Eppendorf, University Cancer Center Hamburg (UCCH), Hamburg, Germany, Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Heidelberg, Germany, Universitätsklinikum Marburg, Klinik für Innere Medizin, Marburg, Germany, Agaplesion Markus Krankenhaus, Hämatologie/Onkologie, Frankfurt, Frankfurt, Germany, Tagestherapiezentrum am ITM, Mannheim, Germany, RKH-Kliniken Ludwigsburg, Klinik für Hämatologie und Onkologie, Ludwigsburg, Germany, Universitätsklinikum Ulm, Klinik für Innere Medizin I, Ulm, Germany, Kantonsspital Schaffhausen, FMH Innere Medizin und Med Onkologie, Schaffhausen, Switzerland, Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt, Germany, Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt Am Main, Germany, Krankenhaus Nordwest, University Cancer Center Frankfurt and Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest, Frankfurt Am Main, Germany, Universitätsmedizin Mannheim, Institut für Pathologie, Mannheim, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: DANTE evaluates atezolizumab in the perioperative treatment of resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma in combination with FLOT. Here, we report interim results. Methods: DANTE is a multicenter, investigator-initiated, phase IIb trial. Patients (pts) with resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N+) were randomized to receive 4+4 cycles of periop. FLOT chemotherapy (arm B) or the same regime with additional atezolizumab at 840 mg, q2w, followed by atezolizumab monotherapy for 8 cycles at 1200 mg, q3w (arm A). The primary endpoint is progression-free survival. The secondary endpoints surgical outcome (pTNM, R0 resection rate and periop. morbidity/mortality), path. regression and safety are reported here. TNM stage was evaluated by local pathologists and path. regression (Becker-Classification) by local and central pathologists. PD-L1 and MSI status were centrally evaluated. Results: In total, 295 pts were randomized (A, 146; B, 149) with baseline characteristics as follows: median age 61y, male 74%, intestinal type 42%, GEJ 61%, cT3/4 77%, N+ 78%. Twenty-five pts (8.5%) were MSI; 50% had PD-L1 CPS ≥1, 23% PD-L1 CPS ≥5 and 15% PD-L1 CPS ≥10. Pre-op FLOT cycles were completed in 93% of pts and post-op cycles in 43% of pts, with no difference between arms. Surgical morbidity (A, 45%; B, 43%) and mortality (overall 2.5%) were comparable between arms, as were R0-resection rates (arm A, 92% vs. arm B, 91%). Downsizing favored arm A vs B (pT0, 23% vs 15%; pN0, 68% vs 54%). Increases in path. regression rates were seen, particularly with higher PD-L1 expression (Table). Conclusions: The analysis shows beneficial effects of atezolizumab combined with FLOT vs FLOT alone on path. stage and path. regression that seem to be more pronounced with higher PD-L1 expression. Sponsor: Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest. EudraCT: 2017-001979-23. Clinical trial information: NCT03421288. Path. regression by PD-L1 expression and MSI status for arms A vs B. Path. reg. for arms A vs B Local assessment Central assessment* TRG1a TRG1a/b TRG1a TRG1a/b All pts (n=295) 24% vs 15% 48% vs 39% 25% vs 24% 49% vs 44% PD-L1 CPS ≥1 (n=146) 26% vs 16% 53% vs 49% 27% vs 25% 54% vs 50% PD-L1 CPS ≥5 (n=67) 30% vs 24% 58% vs 47% 36% vs 27% 55% vs 50% PD-L1 CPS ≥10 (n=45) 38% vs 14% 71% vs 38% 46% vs 24% 71% vs 52% MSI high (n=25) 50% vs 27% 70% vs 47% 50% vs 27% 70% vs 47% *Central assessment was done by one pathologist based on a representative tumor sample.