Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: a multicenter AGEO study

// Juliette Palle 1 , David Tougeron 2 , Astrid Pozet 3 , Emilie Soularue 4 , Pascal Artru 5 , Florence Leroy 6 , Olivier Dubreuil 7 , Matthieu Sarabi 8 , Nicolas Williet 9 , Sylvain Manfredi 10 , Jerome Martin-Babau 11 , Christine Rebischung 12 , Meher Ben Abdelghani 13 , Ludovic Evesque 14 , Johann Dreanic 15 , Vincent Hautefeuille 16 , Samy Louafi 17 , David Sefrioui 18 , Francesco Savinelli 19 , May Mabro 20 , Benoit Rousseau 21 , Cédric Lecaille 22 , Olivier Bouché 23 , Christophe Louvet 24 , Thierry Lecomte 25 , Franck Bonnetain 3 , Julien Taieb 1, 26 and Aziz Zaanan 1, 26 1 Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 2 Department of Gastroenterology, Poitiers University Hospital, Poitiers, France 3 Methodology and Quality of Life in Oncology Unit, INSERM UMR 1098, Besançon University Hospital, Besançon, France 4 Department of Medical Oncology, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 5 Department of Gastroenterology and Digestive Oncology, Jean Mermoz Hospital, Lyon, France 6 Department of Cancer Medicine, Gustave Roussy Institute, Villejuif, France 7 Department of Gastroenterology and Digestive Oncology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 8 Department of Medical Oncology, Léon Bérard Center, Lyon, France 9 Department of Gastroenterology and Digestive Oncology, Saint-Etienne University Hospital, Saint-Priest en Jarez, France 10 Department of Gastroenterology and Digestive Oncology, Rennes University Hospital, Rennes, France 11 Department of Oncology, Morvan University Hospital, Brest, France 12 Department of Oncology, Groupe Hospitalier Mutualiste of Grenoble, Grenoble, France 13 Department of Oncology, Paul Strauss Center, Strasbourg, France 14 Department of Oncology, Antoine Lacassagne Center, Nice, France 15 Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 16 Department of Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France 17 Department of Oncology, Oncology Federation of Essonne, Essonne, France 18 Department of Digestive Oncology, Rouen University Hospital, Rouen, France 19 Department of Medical Oncology, Saint-Joseph Hospital, Paris, France 20 Department of Oncology, Foch Hospital, Suresnes, France 21 Department of Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France 22 Department of Gastroenterology and Digestive Oncology, Polyclinique de Bordeaux Nord, Bordeaux, France 23 Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France 24 Department of Medical Oncology, Mutualiste Montsouris Institute, Paris, France 25 Department of Gastroenterology and Digestive Oncology, Trousseau University Hospital, Tours, France 26 Paris Descartes University, Sorbonne Paris Cité, Paris, France Correspondence to: Aziz Zaanan, email: aziz.zaanan@aphp.fr Keywords: advanced gastric cancer; trastuzumab; HER2; second-line chemotherapy; beyond progression Received: March 01, 2017 Accepted: August 05, 2017 Published: September 08, 2017 ABSTRACT Introduction: Trastuzumab in combination with platinum-based chemotherapy is the standard first-line regimen in HER2-positive advanced gastric cancer. However, there are very few data concerning efficacy of continuing trastuzumab beyond first-line progression. Methods: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received a second-line of chemotherapy with or without trastuzumab after progression on platinum-based chemotherapy plus trastuzumab. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method and compared using log-rank test. The prognostic variables with P values ≤ 0.05 in univariate analysis were eligible for the Cox multivariable regression model. Results: From May 2010 to December 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; ECOG performance status [PS] 0-1, 71.2%). The continuation (n=39) versus discontinuation (n=65) of trastuzumab beyond progression was significantly associated with an improvement of median PFS (4.4 versus 2.3 months; P =0.002) and OS (12.6 versus 6.1 months; P =0.001 ) . In the multivariate analysis including the ECOG PS, number of metastatic sites and measurable disease, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.56; 95% CI, 0.35-0.89; P =0.01) and OS (HR, 0.47; 95% CI, 0.28-0.79; P =0.004). Conclusion: This study suggests that continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer. These results deserve a prospective randomized validation.