Jiménez Fonseca, PaulaCarmona Bayonas, AlbertoMartínez Torron, AlbaAlsina, MariaCustodio, AnaSerra, OlbiaCacho Lavín, DiegoLimon Miron, Maria LuisaSauri, TamaraLópez, FloraVisa, LauraGranja, MónicaMartínez Lago, NievesArrazubi, VirginiaVidal Tocino, RosarioHernandez, RaquelAguado, GemmaCano, Juana MaríaMartín Carnicero, AlfonsoMangas-Izquierdo, MontserratPimentel, PaolaFernández Montes, AnaMacias Declara, IsmaelLongo, FedericoRamchandani, AvinashMartín Richard, MartaHurtado, AliciaAzkarate, AitorHernández Pérez, CarolinaSerrano, RaquelGallego, JavierOn Behalf Of The Agamenon-seom Study Group2021-09-132021-09-132021-01-011758-8359https://hdl.handle.net/2445/179950Background: 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.13 p.application/pdfengcc by-nc (c) Jimenez Fonseca, Paula et al, 2021http://creativecommons.org/licenses/by-nc/3.0/es/Càncer d'estómacQuimioteràpiaStomach cancerChemotherapyinfo:eu-repo/semantics/article2021-09-10info:eu-repo/semantics/openAccess34211587