External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

Autor: Jimenez-Fonseca P; Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Avenida Roma s/n, Oviedo, Spain. palucaji@hotmail.com., Carmona-Bayonas A; Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, University of Murcia, IMIB, CP13/00126, PI17/0050 (ISCIII& FEDER), Murcia, Spain.; Fundación Séneca (04515/GERM/06), Murcia, Spain., Martínez de Castro E; Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain., Custodio A; Medical Oncology Department, Hospital Universitario La Paz, CIBERONC CB16/12/00398, Madrid, Spain., Pericay Pijaume C; Medical Oncology Department, Hospital Universitario Parc Tauli, Sabadell, Spain., Hernandez R; Medical Oncology Department, Hospital Universitario de Canarias, Tenerife, Spain., Aguado G; Medical Oncology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain., Castro Unanua N; Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain., Cano JM; Medical Oncology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain., López F; Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain., Garrido M; Medical Oncology Department, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile., Fernández Montes A; Medical Oncology Department, Complejo Hospitalario de Orense, Orense, Spain., Visa L; Medical Oncology Department, Hospital Universitario El Mar, Barcelona, Spain., Sánchez Cánovas M; Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain., Limón ML; Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain., Martínez Lago N; Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, Coruña, Spain., Pimentel P; Medical Oncology Department, Hospital Santa Lucía, Cartagena, Spain., Hurtado A; Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain., Azkárate A; Medical Oncology Department, Hospital Universitario Son Espases, Mallorca, Spain., Longo F; Medical Oncology Department, Hospital Universitario Ramón and Cajal, Madrid, Spain., Diez M; Medical Oncology Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain., Arias-Martinez A; Pharmacy Department, Hospital Universitario Central de Asturias, Oviedo, Spain., Sauri T; Medical Oncology Department, Hospital Clinic, Barcelona, Spain., Martín Carnicero A; Medical Oncology Department, Hospital San Pedro, Logroño, Spain., Mangas M; Medical Oncology Department, Hospital Galdakao-Usansolo, Galdakao-Usansolo, Spain., Martín Richard M; Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain., Granja M; Medical Oncology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain., Ramchandani A; Medical Oncology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain., Hernández Pérez C; Medical Oncology Department, Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain., Cerdá P; Medical Oncology Department, Centro Médico Tecknon, Barcelona, Spain., Gil-Negrete A; Medical Oncology Department, Hospital Universitario de Donostia, San Sebastián, Spain., Calvo M; Medical Oncology Department, Catalan Institute of Oncology, L'Hospitalet, Spain., Vidal Tocino R; Medical Oncology Department, Complejo Asistencial Universitario de Salamanca, IBSAL, Salamanca, Spain., Gallego J; Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain.
Jazyk: angličtina
Zdroj: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association [Gastric Cancer] 2021 Mar; Vol. 24 (2), pp. 445-456. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1007/s10120-020-01116-x
Abstrakt: 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.
Databáze: MEDLINE
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