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Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer

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Summary

Pembrolizumab treatment is associated with a favorable prognosis in patients with non-small-cell lung cancer (NSCLC). Here, we investigated the associations among pre-treatment clinical factors, baseline overall tumor burden, and development of severe immune-related adverse events (irAEs; grade ≥ 3) after pembrolizumab treatment with or without chemotherapy. We retrospectively examined consecutive patients with advanced NSCLC who received pembrolizumab with or without chemotherapy at Hakodate Goryoukaku Hospital from March 2017 to February 2021. The baseline overall tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions. We defined irAEs as toxicities related to immune checkpoint inhibitors based on the Common Terminology Criteria for Adverse Events, version 5.0. Tumor burden differed significantly between patients with and without severe irAEs (85 vs. 65 mm, p = 0.0367). The cutoff value for overall tumor burden was set to 80 mm. Good performance status (PS = 0) and PD-L1 expression > 80%, but not overall tumor burden, were correlated with severe irAEs, regardless of complementary chemotherapy. The multivariate odds ratios of good PS and high PD-L1 expression for severe irAEs were 3.27 (95% confidence interval [CI]: 1.22–8.77, p = 0.019) and 4.44 (95% CI: 1.59–12.42, p = 0.0044), respectively. Baseline overall tumor burden, good PS, and high PD-L1 expression were associated with severe irAEs in patients with NSCLC treated with first-line pembrolizumab with or without chemotherapy. Patients with these factors should be carefully monitored to prevent irAEs.

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Data availability statement

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

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Hakodate Goryoukaku Hospital, 38-3 Goryoukaku-Cho, Hakodate-shi, Hokkaido, 040-8611, Japan

    Toshiyuki Sumi, Yuta Koshshino, Hiroki Watanabe, Haruhiko Michimata, Daiki Nagayama & Yuichi Yamada

  2. Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Toshiyuki Sumi, Yuta Koshshino, Motoki Sekikawa, Yuta Nagahisa, Keigo Matsuura, Naoki Shijubou, Koki Kamada, Haruhiko Michimata, Daiki Nagayama, Yusuke Tanaka & Hirofumi Chiba

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Contributions

Toshiyuki Sumi conceived the idea of the study. Motoki Sekikawa, Yuta Nagahisa, Keigo Matsuura, Naoki Shijubou, Koki Kamada, Hiroki Watanabe, Yuta Koshino, Daiki Nagayama, Haruhiko Michimata, and Yuichi Yamada developed the statistical analysis plan and conducted statistical analyses. Yusuke Tanaka contributed to the interpretation of the results. Toshiyuki Sumi drafted the original manuscript. Hirofumi Chiba supervised the conduct of this study. All authors reviewed the manuscript draft and revised it critically on intellectual content. All authors read and approved the final manuscript.

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Correspondence to Toshiyuki Sumi.

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This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Institutional Ethics Committee of Hakodate Goryoukaku Hospital (approval no. 2022–019) approved this study.

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Sumi, T., Koshshino, Y., Sekikawa, M. et al. Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. Invest New Drugs 40, 1298–1305 (2022). https://doi.org/10.1007/s10637-022-01310-x

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