Journal Article

EORTC-1203-GITCG - the “INNOVATION”-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group

Heike I. Grabsch, Annelie Elme, Peter C. Thuss-Patience, Florian Lordick, Annemieke Cats, Uwe M. Martens, Anna Dorothea Wagner, Yoon-Koo Kang, Sandrine Marreaud, Markus Moehler, Masanori Tokunaga, Lothar Mueller, Carmela Caballero, Sun Young Rha, Murielle Mauer

2019

Overview

Background 10–20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC. Methods This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined. Two hundred and-fifteen patients from 52 sites in 14 countries will be centrally randomized (1:2:2 ratio) to one of the following treatment arms: Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator’s choice in Europe, and cisplatin/capecitabine in Asia. Experimental arm 1 : CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Adjuvant treatment with T or T + P will continue for 17 cycles in total. Stratification factors are: histology (intestinal/non-intestinal); region (Asia vs Europe); location (GEJ vs non-GEJ); HER2 immunohistochemistry score (IHC 3+ vs IHC 2+/FISH+) and chemotherapy regimen. Primary objective is to detect an increase in the major pathological response rate from 25 to 45% either with CT plus T alone, or with CT plus the combination of T and P. Discussion Depending on the results of the INNOVATION trial, the addition of HER2 targeted treatment with either T or T and P to CT may inform future study designs or become a standard in the perioperative management HER2+ GC. Trial registration This article reports a health care intervention on human participants and was registered on July 10, 2014 under ClinicalTrials.gov identifier: NCT02205047 ; EudraCT: 2014–000722-38.

• Publisher: Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Adenocarcinoma - drug therapy / Adenocarcinoma - mortality / Adult / Aged / Aged, 80 and over / Antibodies, Monoclonal, Humanized / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Agents / Antineoplastic Agents - therapeutic use / Antineoplastic Agents, Immunological / Antineoplastic Agents, Immunological - administration & dosage / Antineoplastic Agents, Immunological - therapeutic use / Antineoplastic Combined Chemotherapy Protocols / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomedical and Life Sciences / Biomedicine / BREAST-CANCER / Cancer / Cancer metastasis / Cancer patients / Cancer Research / Cancer therapies / Cancer treatment / CAPECITABINE / Capecitabine - therapeutic use / Chemotherapy / Cisplatin / Cisplatin - therapeutic use / Clinical trials / Comparative analysis / DOCETAXEL / Dosage and administration / Drug delivery / Drug therapy / Epidermal growth factor / ErbB-2 protein / Esophageal cancer / Esophageal Neoplasms / Esophageal Neoplasms - drug therapy / Esophageal Neoplasms - mortality / Esophagogastric Junction / Esophagogastric Junction - pathology / Esophagus / Female / Fluorouracil / Fluorouracil - therapeutic use / Follow-Up Studies / Gastric cancer / Gastric cancer; Gastro-esophageal junction cancer; HER2; Perioperative chemotherapy; Pertuzumab; Trastuzumab / Gastro-esophageal junction cancer / Gastrointestinal cancer / Gastrointestinal system / Gastrointestinal tract / Health Promotion and Disease Prevention / HER2 / Humans / Immunohistochemistry / Immunotherapy / Intestine / Labels / Male / Medical and radiation oncology / Medicine/Public Health / Metastases / Metastasis / Middle Aged / Monoclonal antibodies / NEOADJUVANT CHEMOTHERAPY / Neoadjuvant Therapy / Neoplasms. Tumors. Oncology. Including cancer and carcinogens / Netherlands / Oncology / OPEN-LABEL / OXALIPLATIN / Patients / Perioperative chemotherapy / Perioperative Period / Pertuzumab / Progression-Free Survival / Prospective Studies / RC254-282 / Receptor, ErbB-2 / Receptor, ErbB-2 - metabolism / REGRESSION / Republic of Korea / Response rates / Stomach cancer / Stomach Neoplasms / Stomach Neoplasms - drug therapy / Stomach Neoplasms - mortality / Studies / Study Protocol / SURGERY / Surgical Oncology / Surgical outcomes / Targeted cancer therapy / Taxotere / Trastuzumab / Trastuzumab - administration & dosage / Trastuzumab - therapeutic use / Treatment Outcome / Tumors / Young Adult