Jimenez-Fonseca, PaulaCarmona-Bayonas, AlbertoMartinez-Torron, AlbaAlsina, MariaCustodio, AnaSerra, OlbiaCacho Lavin, DiegoLimón, María LuisaSauri, TamaraLópez, FloraVisa, LauraGranja, MónicaMartínez Lago, NievesArrazubi, VirginiaVidal Tocino, RosarioHernandez, RaquelAguado, GemaCano, Juana MaríaMartín Carnicero, AlfonsoMangas, MonserratPimentel, PaolaFernández Montes, AnaMacias Declara, IsmaelLongo, FedericoRamchandani, AvinashMartín Richard, MartaHurtado, AliciaAzkarate, AitorHernández Pérez, CarolinaSerrano, RaquelGallego, JavierAGAMENON-SEOM study group2025-01-072025-01-072021-06-171758-8340https://hdl.handle.net/10668/27514Trastuzumab 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. 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. 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  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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/HER2chemotherapyexternal validitygastric canceroxaliplatintrastuzumabresearch article34211587open access10.1177/17588359211019672PMC8216357https://journals.sagepub.com/doi/pdf/10.1177/17588359211019672https://pmc.ncbi.nlm.nih.gov/articles/PMC8216357/pdf