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Research Papers:

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

Juliette Palle, David Tougeron, Astrid Pozet, Emilie Soularue, Pascal Artru, Florence Leroy, Olivier Dubreui, Matthieu Sarabi, Nicolas Williet, Sylvain Manfredi, Jerome Martin-Babau, Christine Rebischung, Meher Ben Abdelghani, Ludovic Evesque, Johann Dreanic, Vincent Hautefeuille, Samy Louafi, David Sefrioui, Francesco Savinelli, May Mabro, Benoit Rousseau, Cédric Lecaille, Olivier Bouché, Christophe Louvet, Thierry Lecomte, Franck Bonnetain, Julien Taieb and Aziz Zaanan _

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Oncotarget. 2017; 8:101383-101393. https://doi.org/10.18632/oncotarget.20711

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Abstract

Juliette Palle1, David Tougeron2, Astrid Pozet3, Emilie Soularue4, Pascal Artru5, Florence Leroy6, Olivier Dubreuil7, Matthieu Sarabi8, Nicolas Williet9, Sylvain Manfredi10, Jerome Martin-Babau11, Christine Rebischung12, Meher Ben Abdelghani13, Ludovic Evesque14, Johann Dreanic15, Vincent Hautefeuille16, Samy Louafi17, David Sefrioui18, Francesco Savinelli19, May Mabro20, Benoit Rousseau21, Cédric Lecaille22, Olivier Bouché23, Christophe Louvet24, Thierry Lecomte25, Franck Bonnetain3, Julien Taieb1,26 and Aziz Zaanan1,26

1Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

2Department of Gastroenterology, Poitiers University Hospital, Poitiers, France

3Methodology and Quality of Life in Oncology Unit, INSERM UMR 1098, Besançon University Hospital, Besançon, France

4Department of Medical Oncology, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

5Department of Gastroenterology and Digestive Oncology, Jean Mermoz Hospital, Lyon, France

6Department of Cancer Medicine, Gustave Roussy Institute, Villejuif, France

7Department of Gastroenterology and Digestive Oncology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

8Department of Medical Oncology, Léon Bérard Center, Lyon, France

9Department of Gastroenterology and Digestive Oncology, Saint-Etienne University Hospital, Saint-Priest en Jarez, France

10Department of Gastroenterology and Digestive Oncology, Rennes University Hospital, Rennes, France

11Department of Oncology, Morvan University Hospital, Brest, France

12Department of Oncology, Groupe Hospitalier Mutualiste of Grenoble, Grenoble, France

13Department of Oncology, Paul Strauss Center, Strasbourg, France

14Department of Oncology, Antoine Lacassagne Center, Nice, France

15Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

16Department of Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France

17Department of Oncology, Oncology Federation of Essonne, Essonne, France

18Department of Digestive Oncology, Rouen University Hospital, Rouen, France

19Department of Medical Oncology, Saint-Joseph Hospital, Paris, France

20Department of Oncology, Foch Hospital, Suresnes, France

21Department of Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France

22Department of Gastroenterology and Digestive Oncology, Polyclinique de Bordeaux Nord, Bordeaux, France

23Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France

24Department of Medical Oncology, Mutualiste Montsouris Institute, Paris, France

25Department of Gastroenterology and Digestive Oncology, Trousseau University Hospital, Tours, France

26Paris 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.


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