Abstract

BackgroundThe 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.MethodsThe 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.ResultThe 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.ConclusionOur 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.

Highlights

  • We have observed that the use of triplets with docetaxel increased progression-free survival (PFS) by 27% and overall survival (OS) by 19% in patients with advanced gastric cancer (AGC)

  • The AGAMENON registry reproduces the temporal trend seen in successive randomized clinical trials (RCTs) with docetaxel combined with platin-fluoropyrimidine (DPF) in first line [8, 9], making it a worthwhile instrument to explore the reasons for this weakening of effect and ascertain those patient groups for whom DPF combinations are still effective

  • While our data indicate that the most plausible explanation is the introduction of taxanes in second line, other aspects must be born in mind, such as the increased popularity of the oxaliplatin-containing doublet, which is observed in the literature [35, 36]

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Summary

Introduction

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. 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

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