Paula Jimenez-Fonseca1, Alberto Carmona-Bayonas2,3, Eva Martínez de Castro4, Ana Custodio5, Carles Pericay Pijaume6, Raquel Hernandez7, Gema Aguado8, Natalia Castro Unanua9, Juana María Cano10, Flora López11, Marcelo Garrido12, Ana Fernández Montes13, Laura Visa14, Manuel Sánchez Cánovas15, María Luisa Limón16, Nieves Martínez Lago17, Paola Pimentel18, Alicia Hurtado19, Aitor Azkárate20, Federico Longo21, Marc Diez22, Aranzazu Arias-Martinez23, Tamara Sauri24, Alfonso Martín Carnicero25, Monserrat Mangas26, Marta Martín Richard27, Mónica Granja28, Avinash Ramchandani29, Carolina Hernández Pérez30, Paula Cerdá31, Aitziber Gil-Negrete32, Mariona Calvo33, Rosario Vidal Tocino34, Javier Gallego35. 1. Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Avenida Roma s/n, Oviedo, Spain. palucaji@hotmail.com. 2. Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, University of Murcia, IMIB, CP13/00126, PI17/0050 (ISCIII& FEDER), Murcia, Spain. 3. Fundación Séneca (04515/GERM/06), Murcia, Spain. 4. Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain. 5. Medical Oncology Department, Hospital Universitario La Paz, CIBERONC CB16/12/00398, Madrid, Spain. 6. Medical Oncology Department, Hospital Universitario Parc Tauli, Sabadell, Spain. 7. Medical Oncology Department, Hospital Universitario de Canarias, Tenerife, Spain. 8. Medical Oncology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain. 9. Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. 10. Medical Oncology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. 11. Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain. 12. Medical Oncology Department, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile. 13. Medical Oncology Department, Complejo Hospitalario de Orense, Orense, Spain. 14. Medical Oncology Department, Hospital Universitario El Mar, Barcelona, Spain. 15. Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. 16. Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain. 17. Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, Coruña, Spain. 18. Medical Oncology Department, Hospital Santa Lucía, Cartagena, Spain. 19. Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 20. Medical Oncology Department, Hospital Universitario Son Espases, Mallorca, Spain. 21. Medical Oncology Department, Hospital Universitario Ramón and Cajal, Madrid, Spain. 22. Medical Oncology Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 23. Pharmacy Department, Hospital Universitario Central de Asturias, Oviedo, Spain. 24. Medical Oncology Department, Hospital Clinic, Barcelona, Spain. 25. Medical Oncology Department, Hospital San Pedro, Logroño, Spain. 26. Medical Oncology Department, Hospital Galdakao-Usansolo, Galdakao-Usansolo, Spain. 27. Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain. 28. Medical Oncology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain. 29. Medical Oncology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain. 30. Medical Oncology Department, Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain. 31. Medical Oncology Department, Centro Médico Tecknon, Barcelona, Spain. 32. Medical Oncology Department, Hospital Universitario de Donostia, San Sebastián, Spain. 33. Medical Oncology Department, Catalan Institute of Oncology, L'Hospitalet, Spain. 34. Medical Oncology Department, Complejo Asistencial Universitario de Salamanca, IBSAL, Salamanca, Spain. 35. Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain.
Abstract
BACKGROUND: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. METHODS: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. RESULT: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. CONCLUSION: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.
BACKGROUND: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. METHODS: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. RESULT: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. CONCLUSION: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.
Authors: Karel G M Moons; Andre Pascal Kengne; Diederick E Grobbee; Patrick Royston; Yvonne Vergouwe; Douglas G Altman; Mark Woodward Journal: Heart Date: 2012-03-07 Impact factor: 5.994
Authors: Duminda N Wijeysundera; Peter C Austin; Janet E Hux; W Scott Beattie; Andreas Laupacis Journal: J Clin Epidemiol Date: 2008-10-23 Impact factor: 6.437
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Authors: Laura Visa; Paula Jiménez-Fonseca; Elena Asensio Martínez; Raquel Hernández; Ana Custodio; Manuel Garrido; Antonio Viudez; Elvira Buxo; Ignacio Echavarria; Juana María Cano; Ismael Macias; Montserrat Mangas; Eva Martínez de Castro; Teresa García; Felipe Álvarez Manceñido; Ana Fernández Montes; Aitor Azkarate; Federico Longo; Asunción Díaz Serrano; Carlos López; Alicia Hurtado; Paula Cerdá; Raquel Serrano; Aitziber Gil-Negrete; Alfonso Martín Carnicero; Paola Pimentel; Avinash Ramchandani; Alberto Carmona-Bayonas Journal: J Geriatr Oncol Date: 2017-12-11 Impact factor: 3.599
Authors: Almudena Cotes Sanchís; Javier Gallego; Raquel Hernandez; Virginia Arrazubi; Ana Custodio; Juana María Cano; Gema Aguado; Ismael Macias; Carlos Lopez; Flora López; Laura Visa; Marcelo Garrido; Nieves Martínez Lago; Ana Fernández Montes; María Luisa Limón; Aitor Azkárate; Paola Pimentel; Pablo Reguera; Avinash Ramchandani; Juan Diego Cacho; Alfonso Martín Carnicero; Mónica Granja; Marta Martín Richard; Carolina Hernández Pérez; Alicia Hurtado; Olbia Serra; Elvira Buxo; Rosario Vidal Tocino; Paula Jimenez-Fonseca; Alberto Carmona-Bayonas Journal: PLoS One Date: 2020-07-31 Impact factor: 3.240
Authors: Sena Valcarcel; Javier Gallego; Paula Jimenez-Fonseca; Marc Diez; Eva Martínez de Castro; Raquel Hernandez; Virginia Arrazubi; Ana Custodio; Juana María Cano; Ana Fernández Montes; Ismael Macias; Laura Visa; Aitana Calvo; Rosario Vidal Tocino; Nieves Martínez Lago; María Luisa Limón; Mónica Granja; Mireia Gil; Paola Pimentel; Lola Macia-Rivas; Carolina Hernández Pérez; Montserrat Mangas; Alfonso Martín Carnicero; Paula Cerdà; Lucía Gomez Gonzalez; Francisco Garcia Navalon; Mª Dolores Mediano Rambla; Marta Martin Richard; Alberto Carmona-Bayonas Journal: J Cancer Res Clin Oncol Date: 2022-08-30 Impact factor: 4.322
Authors: J Gallego Plazas; A Arias-Martinez; A Lecumberri; E Martínez de Castro; A Custodio; J M Cano; R Hernandez; A F Montes; I Macias; A Pieras-Lopez; M Diez; L Visa; R V Tocino; N Martínez Lago; M L Limón; M Gil; P Pimentel; M Mangas; M Granja; A M Carnicero; C Hernández Pérez; L G Gonzalez; P Jimenez-Fonseca; A Carmona-Bayonas Journal: ESMO Open Date: 2022-06-14
Authors: David Zaragoza-Huesca; Pedro Garrido-Rodríguez; Paula Jiménez-Fonseca; Eva Martínez de Castro; Manuel Sánchez-Cánovas; Laura Visa; Ana Custodio; Ana Fernández-Montes; Julia Peñas-Martínez; Patricia Morales Del Burgo; Javier Gallego; Ginés Luengo-Gil; Vicente Vicente; Irene Martínez-Martínez; Alberto Carmona-Bayonas Journal: Biomedicines Date: 2022-01-11