External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?
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ORIGINAL ARTICLE
External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit? 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 Received: 6 June 2020 / Accepted: 23 August 2020 © The Author(s) 2020
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. Keywords Bayesian model · Chemotherapy · Gastric cancer · Docetaxel · Survival
Introduction External validity or the inferential generalizability of randomized clinical trials (RCTs) refers to the appropriateness of extrapolating trial outcomes from one population to another. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10120-020-01116-x) contains supplementary materi
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