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
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spelling External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinomadata from the AGAMENON-SEOM registryJiménez Fonseca, Paula|||0000-0003-4592-3813Carmona-Bayonas, Alberto|||0000-0002-1930-9660Martinez-Torron, AlbaAlsina, Maria|||0000-0003-4835-7159Custodio, AnaSerra, OlbiaCacho Lavín, DiegoLimón, María Luisa|||0000-0003-4409-3029Saurí Nadal, Tamara|||0000-0002-7479-5120López, FloraVisa, Laura|||0000-0002-3409-8857Granja, MónicaMartínez Lago, Nieves|||0000-0002-0408-6871Arrazubi, VirginiaVidal Tocino, Rosario|||0000-0002-0588-2001Hernandez, RaquelAguado, GemaCano, Juana María|||0000-0002-2493-0988Martín Carnicero, Alfonso|||0000-0002-8564-2875Mangas, MontserratPimentel, Paola|||0000-0002-1676-5724Fernández Montes, Ana|||0000-0003-4630-5830Macias Declara, IsmaelLongo, Federico|||0000-0003-0902-2188Ramchandani, Avinash|||0000-0002-9754-3903Martín-Richard, Marta|||0000-0003-4933-2463Hurtado-Nuño, Alicia|||0000-0003-0082-8863Azkárate, Aitor|||0000-0002-6805-158XHernández Pérez, CarolinaSerrano, RaquelGallego Plazas, Javier|||0000-0002-0584-1242ChemotherapyExternal validityGastric cancerHER2OxaliplatinTrastuzumabBackground: 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. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/271898https://dx.doi.org/urn:doi:10.1177/17588359211019672reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2718982026-06-06T12:50:31Z
dc.title.none.fl_str_mv External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
data from the AGAMENON-SEOM registry
title External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
spellingShingle External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
Jiménez Fonseca, Paula|||0000-0003-4592-3813
Chemotherapy
External validity
Gastric cancer
HER2
Oxaliplatin
Trastuzumab
title_short External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
title_full External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
title_fullStr External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
title_full_unstemmed External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
title_sort External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma
dc.creator.none.fl_str_mv 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
author Jiménez Fonseca, Paula|||0000-0003-4592-3813
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Chemotherapy
External validity
Gastric cancer
HER2
Oxaliplatin
Trastuzumab
topic Chemotherapy
External validity
Gastric cancer
HER2
Oxaliplatin
Trastuzumab
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/271898
https://dx.doi.org/urn:doi:10.1177/17588359211019672
url https://ddd.uab.cat/record/271898
https://dx.doi.org/urn:doi:10.1177/17588359211019672
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
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reponame_str Dipòsit Digital de Documents de la UAB
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