Abstract 3780
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.
Trial design
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 May 2019, a total of 60 patients have been randomized. ClinicalTrials.gov Identifier: NCT03421288.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IKF Klinische Krebsforschung GmbH am Krankenhaus Nordwest.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
S. Al-Batran: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Nordic Bioscience; Advisory / Consultancy: Merck Sharp & Dohme; Leadership role, Shareholder / Stockholder / Stock options: IKF Klinische Krebsforschung GmbH; Speaker Bureau / Expert testimony: AIO gGmbH; Speaker Bureau / Expert testimony: MCI group; Speaker Bureau / Expert testimony: Forum für Medizinische Fortbildung; Speaker Bureau / Expert testimony: promedicis; Research grant / Funding (self): Medac; Research grant / Funding (self): Hospira; Research grant / Funding (self): Sanofi; Research grant / Funding (self): German Cancer Aid; Research grant / Funding (self): German Research Foundation; Research grant / Funding (self): Federal Ministry of Education and Research of Germany; Research grant / Funding (self): Vifor Pharma. R.D. Hofheinz: Honoraria (self), Advisory / Consultancy: Brystol-Myers-Squibb. S. Lorenzen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Lilly; Advisory / Consultancy: Servier; Advisory / Consultancy: Sanofi/Aventis; Advisory / Consultancy: Celgene; Advisory / Consultancy: MSD Oncology. A. Wicki: Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Swiss Tumour Profiler Consortium. P.C. Thuss-Patience: Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Teva; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Astellas. D. Pink: Full / Part-time employment: Helios Kliniken GmbH; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Clinigen; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): PharmaMar. E. Goekkurt: Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Roche Pharma AG; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: Servier. H. Schmalenberg: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Archigen Biotech. J.J. Talbot: Full / Part-time employment: F. Hoffmann-La Roche, Ltd. T.O. Goetze: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Servier; Speaker Bureau / Expert testimony: MCI; Research grant / Funding (self): DFG- German Research Foundation; Research grant / Funding (self): Gemeinsamer Deutscher Bundesausschuß. N. Homann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: SERVIER; Advisory / Consultancy: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony: Merck. All other authors have declared no conflicts of interest.
Resources from the same session
3006 - Nal-iri/lv5-fu versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study.
Presenter: Violaine Randrian
Session: Poster Display session 2
Resources:
Abstract
3697 - The expression of Versican and its role in pancreatic neuroendocrine tumor
Presenter: Zhao Sun
Session: Poster Display session 2
Resources:
Abstract
6073 - Characteristics of patients with thyroid carcinoma in the united states
Presenter: Dina El-Habashy
Session: Poster Display session 2
Resources:
Abstract
2124 - The discrimination of pituitary adenomas and craniopharyngioma on MRI: from image features to texture features
Presenter: Hanyue Xu
Session: Poster Display session 2
Resources:
Abstract
3786 - Proportion of Peripheral Lymphocyte Subsets Correlates with the Progression-free Survival and Metastatic Status of Pancreatic Neuroendocrine Tumor Patients
Presenter: Yitao Gong
Session: Poster Display session 2
Resources:
Abstract
2263 - Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma
Presenter: Enas Elkhouly
Session: Poster Display session 2
Resources:
Abstract
4386 - SILVELUL Project: Immunohistochemical panel analyses as potential predictive and prognostic factors in Pancreatic Neuroendocrine Tumors (PanNET) Treated with CAPTEM or Everolimus
Presenter: Ana De Jesus-Acosta
Session: Poster Display session 2
Resources:
Abstract
2302 - Carcinoid heart disease (CHD): the CRUSOE-NETs, a prospective cohort study from the French Group of Endocrine Tumors (GTE)
Presenter: Kathleen Dekeister Geoffroy
Session: Poster Display session 2
Resources:
Abstract
5749 - Safety of high doses of somatostatin analogs in well differentiated NENs in elderly
Presenter: Massimiliano Cani
Session: Poster Display session 2
Resources:
Abstract
3931 - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract