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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Cytostatic Therapy | Research

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint

Authors: Zewei Zhang, Chunxia Xie, Tiantian Gao, Yuxian Yang, Yong Yang, Lei Zhao

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy.

Methods

Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation.

Results

PFS correlated moderately with OS in the retrospective cohort (Kendall’s Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group.

Conclusion

In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.
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Metadata
Title
Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint
Authors
Zewei Zhang
Chunxia Xie
Tiantian Gao
Yuxian Yang
Yong Yang
Lei Zhao
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10613-y

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