Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.

Authors

null

Salah-Eddin Al-Batran

Institute of Clinical Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany

Salah-Eddin Al-Batran , Claudia Pauligk , Ralf Hofheinz , Sylvie Lorenzen , Andreas Wicki , Alexander Rheinhard Siebenhuener , Michael Schenk , Manfred Welslau , Vera Heuer , Eray Goekkurt , Harald Schmalenberg , Peter C. Thuss-Patience , Lisa Waberer , Jonathan Talbot , Thorsten Oliver Goetze , Nils Homann

Organizations

Institute of Clinical Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany, University Cancer Center Frankfurt, Institut für Klinisch-Onkologische Forschung and IKF Klinische Krebsforschung GmbH am Krankenhaus Nordwest, Frankfurt, Germany, University Medical Center Mannheim, Tagestherapiezentrum am ITM, Mannheim, Germany, Third Department of Internal Medicine (Hematology/Medical Oncology), Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany, Universitätsspital Basel, Basel, Switzerland, Klinik für Medizinische Onkologie und Hämatologie, UniversitätsSpital Zürich, Zurich, Switzerland, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany, Klinikum Aschaffenburg, Medizinische Klinik II, Aschaffenburg, Germany, MVZ St. Anna Hospital, Herne, Germany, Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Facharztzentrum Eppendorf, Hamburg, Germany, Krankenhaus Dresden-Friedrichstadt, IV. Medizinische Klinik, Dresden, Germany, Charité–University Medicine Berlin, Department of Haematology, Oncology and Tumorimmunology, Berlin, Germany, IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany, F. Hoffmann-La Roche Ltd., Basel, Switzerland, MED. Klinik II, Klinikum Wolfsburg, Wolfsburg, Germany

Research Funding

Pharmaceutical/Biotech Company

Background: Perioperative FLOT chemotherapy has become a standard of care for locally advanced, resectable gastric cancer and adenocarcinoma of the GEJ. However, patient outcomes are still unsatisfactory and 5-year survival in T3-4 or nodal positive disease is still around 50%. Targeting the PD-1/PD-L1 pathway has proven active in different cancers, including esophagogastric cancer, and was associated with response rates in the 10-15% range in unselected, heavily pre-treated gastric cancer patients. Atezolizumab is a PD-L1 inhibitor with established efficacy and tolerability profiles. This study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with FLOT. Methods: This is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Eligibility status is centrally evaluated. Patients are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m²) followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS) as assessed by the Kaplan-Meier-Method. The statistical design is based on a target HR of 0.68, a power of 0.8, and a significance level of p< 0.05 (1-sided log rank test). A total of 295 patients will be randomized. Main secondary endpoints are rates of centrally assessed pathological regression (rates of complete and nearly complete pathological regression), overall survival, R0 resection, and safety. Recruitment started in Sept 2018; by February 2019, a total of 27 patients have been randomized. Clinical trial information: NCT03421288

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal (Noncolorectal) Cancer

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Esophageal or Gastric Cancer

Clinical Trial Registration Number

NCT03421288

Citation

J Clin Oncol 37, 2019 (suppl; abstr TPS4142)

DOI

10.1200/JCO.2019.37.15_suppl.TPS4142

Abstract #

TPS4142

Poster Bd #

246b

Abstract Disclosures

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