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Efficacy of immune checkpoint inhibitors in younger patients with non-small cell lung cancer

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Abstract

Purpose

Because patients younger than 40 years are rarely enrolled in clinical trials in non-small cell lung cancer (NSCLC), their survival benefit of immune checkpoint inhibitors (ICIs) needs to be clarified.

Methods

The National Cancer Database was queried for patients who were diagnosed with stage IV NSCLC between 2016 and 2018. ICIs were administered in the first-line setting. The overall survival (OS) of patients with stage IV NSCLC according to the receipt of ICIs was compared in different age groups (< 40, 40–49, 50–59, 60–69, 70–79, and ≥ 80 years). Multivariate analyses identified the clinical characteristics predictive of OS. Propensity score matching (PSM) was conducted to reduce the biases arising from clinical characteristics.

Results

This study included 126,476 patients with stage IV NSCLC. In univariate analysis, ICI treatment was not associated with a survival benefit in patients younger than 40 years with stage IV NSCLC relative to their ICI-naïve counterparts after PSM (median OS: 24.2 months vs. 24.0 months, hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.81–1.27, P = 0.9031). Multivariate analysis revealed that ICI use was not an independent predictor of OS in patients with stage IV NSCLC < 40 years old (HR = 0.96, 95% CI = 0.76–1.21, P = 0.7230). Sequential improvement of the HR was observed with increasing age.

Conclusion

Our study suggested a poor survival benefit of ICIs in stage IV NSCLC patients younger than 40 years old, which should be validated in prospective studies.

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Data availability

Data can be available upon request to NCDB.

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Acknowledgements

We thank Joe Barber Jr., PhD, from Edanz (https://jp.edanz.com/ac) and Gregory Wilding for editing a draft of this manuscript and technical assistance, respectively.

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Authors and Affiliations

  1. Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, 879-5593, Japan

    Shinkichi Takamori

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka, 812-0054, Japan

    Shinkichi Takamori

  3. Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

    Mototsugu Shimokawa

  4. Division of Hematology Oncology, Penn State Cancer Institute, 500 University Dr, Hershey, PA, 17033, USA

    Takefumi Komiya

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  1. Shinkichi Takamori
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Contributions

ST wrote the mαin manuscript text, TK. performed statistical analysis, and MS supervised all the statistical analysis. All authors reviewed the manuscript.

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Correspondence to Takefumi Komiya.

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Conflict of interest

Takefumi Komiya received institutional research funding from Merck and Gilead and advisory fees from Regeneron and Novocure. All authors declare no conflicts of interest associated with this study.

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Based on the use of only de-identified data, the study was exempted by the Parkview institutional review board.

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432_2023_5167_MOESM1_ESM.pptx

Supplementary Fig. 1. The Kaplan–Meier curve of overall survival among patients with stage IV non-small cell lung cancer according to immune checkpoint inhibitor use. Supplementary file1 (PPTX 39 KB)

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Takamori, S., Shimokawa, M. & Komiya, T. Efficacy of immune checkpoint inhibitors in younger patients with non-small cell lung cancer. J Cancer Res Clin Oncol 149, 13175–13184 (2023). https://doi.org/10.1007/s00432-023-05167-2

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