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Magnitude of advantage in tumor response contributes to a better correlation between treatment effects on overall survival and progression-free survival: a literature-based meta-analysis of clinical trials in patients with metastatic colorectal cancer

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Abstract

Background

Although it is suggested that the endpoints originated from the concept of tumor shrinkage dynamics, such as early tumor shrinkage and depth of response, are strongly associated with overall survival (OS) in patients with metastatic colorectal cancer (mCRC), they are yet to be validated as a single surrogate endpoint of OS by themselves. This study aimed to investigate the impact of advantage in tumor response on the correlation between treatment effects on progression-free survival (PFS) and OS in mCRC patients.

Methods

Based on an electronic search, we identified randomized controlled trials of first-line therapy for mCRC. The impact of advantage in objective response rate (ORR) on the correlation between treatment effects on PFS and OS was evaluated based on Spearman correlation coefficients (rs).

Results

Forty-seven trials with a total of 24,018 patients were identified. The hazard ratio for PFS showed a relatively higher correlation with that for OS (rs = 0.63) when the trials were limited to those that demonstrated a larger difference in ORR, compared to the case for trials that demonstrated a smaller difference (rs = 0.32). This tendency was also observed in the subgroup analysis stratified by the types of treatment agents (targeted or non-targeted).

Conclusions

The magnitude of advantage in tumor response was suggested to contribute to a better prediction of OS benefit based on PFS in patients with mCRC. The accuracy of OS estimation in mCRC is expected to be improved by considering the degree of tumor shrinkage in conjunction with PFS.

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Acknowledgements

We would like to thank Kae Nakashima, Ph.D., for her support in English editing.

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

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  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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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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Correspondence to Yosuke Yoshida.

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All authors have no conflicts of interest that are directly relevant to this research. Yosuke Yoshida is an employee of MSD K.K., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Yoshida, Y., Kaneko, M. & Narukawa, M. Magnitude of advantage in tumor response contributes to a better correlation between treatment effects on overall survival and progression-free survival: a literature-based meta-analysis of clinical trials in patients with metastatic colorectal cancer. Int J Clin Oncol 25, 851–860 (2020). https://doi.org/10.1007/s10147-020-01619-8

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