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Impact of Advantage in Tumor Response on the Correlation Between Progression-Free Survival and Overall Survival: Meta-Analysis of Clinical Trials in Patients with Advanced Non-Small Cell Lung Cancer

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Abstract

Background

Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) in patients with advanced non-small cell lung cancer.

Objective

This study aimed to investigate an impact of advantage in tumor response on the correlation between PFS and OS in advanced non-small cell lung cancer.

Methods

Based on a literature search, we identified randomized controlled trials of first-line therapy for advanced non-small cell lung cancer. The impact of absolute difference in objective response rate between treatment arms on the correlation between hazard ratios (HRs) for PFS and OS was evaluated based on Spearman rank correlation coefficients.

Results

Sixty trials with a total of 29,134 patients were identified. The HR for PFS showed a relatively higher correlation with HR for OS (rs = 0.75) when the trials were limited to those that demonstrated a larger advantage in objective response rate, compared with the case for trials that demonstrated a smaller advantage (rs = 0.66). This tendency was also observed in the subgroup analysis stratified by the types of treatment agents (non-targeted, anti-angiogenic, and immunotherapy) except for the group of epidermal growth factor receptor-targeted agents.

Conclusions

The magnitude of advantage in tumor response was suggested to contribute to a better prediction of OS-HR based on PFS-HR in clinical trials in patients with advanced non-small cell lung cancer.

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Authors and Affiliations

  1. Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo, 108-8641, Japan

    Yosuke Yoshida, Masayuki Kaneko & Mamoru Narukawa

  2. MSD K.K., a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA

    Yosuke Yoshida

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  1. Yosuke Yoshida
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  2. Masayuki Kaneko
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  3. Mamoru Narukawa
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Correspondence to Yosuke Yoshida.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

Yosuke Yoshida, Masayuki Kaneko, and Mamoru Narukawa have no conflicts of interest that are directly relevant to the content of this study. Yosuke Yoshida is an employee of MSD K.K., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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All statistical analyses were performed using R software version 3.5.0 (http://www.r-project.org).

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by YY and MK. The first draft of the manuscript was written by YY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Yoshida, Y., Kaneko, M. & Narukawa, M. Impact of Advantage in Tumor Response on the Correlation Between Progression-Free Survival and Overall Survival: Meta-Analysis of Clinical Trials in Patients with Advanced Non-Small Cell Lung Cancer. Pharm Med 35, 81–92 (2021). https://doi.org/10.1007/s40290-021-00383-y

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