External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer t...

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Autores: Jiménez Fonseca, Paula|||0000-0003-4592-3813, Carmona-Bayonas, Alberto|||0000-0002-1930-9660, Martinez-Torron, Alba, Alsina, Maria|||0000-0003-4835-7159, Custodio, Ana, Serra, Olbia, Cacho Lavín, Diego, Limón, María Luisa|||0000-0003-4409-3029, Saurí Nadal, Tamara|||0000-0002-7479-5120, López, Flora, Visa, Laura|||0000-0002-3409-8857, Granja, Mónica, Martínez Lago, Nieves|||0000-0002-0408-6871, Arrazubi, Virginia, Vidal Tocino, Rosario|||0000-0002-0588-2001, Hernandez, Raquel, Aguado, Gema, Cano, Juana María|||0000-0002-2493-0988, Martín Carnicero, Alfonso|||0000-0002-8564-2875, Mangas, Montserrat, Pimentel, Paola|||0000-0002-1676-5724, Fernández Montes, Ana|||0000-0003-4630-5830, Macias Declara, Ismael, Longo, Federico|||0000-0003-0902-2188, Ramchandani, Avinash|||0000-0002-9754-3903, Martín-Richard, Marta|||0000-0003-4933-2463, Hurtado-Nuño, Alicia|||0000-0003-0082-8863, Azkárate, Aitor|||0000-0002-6805-158X, Hernández Pérez, Carolina, Serrano, Raquel, Gallego Plazas, Javier|||0000-0002-0584-1242
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:271898
Acceso en línea:https://ddd.uab.cat/record/271898
https://dx.doi.org/urn:doi:10.1177/17588359211019672
Access Level:acceso abierto
Palabra clave:Chemotherapy
External validity
Gastric cancer
HER2
Oxaliplatin
Trastuzumab
Descripción
Sumario:Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.

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