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Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non–small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study

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Summary

Associations between treatment outcomes of immune checkpoint inhibitors and metastatic sites in advanced non-small cell lung cancer (NSCLC) are not well known. Therefore, this multicenter retrospective study aimed to investigate the predictive factors of metastatic sites after first-line pembrolizumab treatment for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. We retrospectively analyzed advanced NSCLC patients with a PD-L1 TPS ≥50% who underwent first-line pembrolizumab therapy at 11 institutions between February 2017 and April 2018. Clinical data collected from medical records included metastatic sites at the time of pembrolizumab treatment. Treatment outcomes of pembrolizumab were assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. In total, 213 patients were included in the study. The median age was 71 years (range 39–91 years). Of the 213 patients, 176 (83%) were men and 172 (81%) had an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0–1. The most common metastases were thoracic lymph node metastasis (77%), intrapulmonary metastasis (31%), bone metastasis (28%), and malignant pleural effusion (26%). On multivariate analysis, a poor ECOG-PS score (hazard ratio: 1.95, 95.0% confidence interval: 1.25–3.04; P = 0.003) and malignant pleural effusion (hazard ratio: 1.52, 95.0% confidence interval: 1.01–2.29; P = 0.043) were independent predictors of shorter progression-free survival in patients treated with pembrolizumab. For NSCLC patients with malignant pleural effusion, pembrolizumab monotherapy is not a suitable first-line treatment because of its insufficient effectiveness, even though their PD-L1 TPS was high.

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Acknowledgements

We are grateful to all the patients and investigators in this study. 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 Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemachi, Osaka, 541-8567, Japan

    Hayato Kawachi, Motohiro Tamiya & Toru Kumagai

  2. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan

    Akihiro Tamiya & Seigo Ishii

  3. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan

    Katsuya Hirano & Hirotaka Matsumoto

  4. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan

    Yasushi Fukuda & Toshihide Yokoyama

  5. Department of Respiratory Medicine, National Hospital Organization Himeji Medical Center, Himeji, Japan

    Ryota Kominami

  6. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan

    Daichi Fujimoto & Kazutaka Hosoya

  7. Department of Thoracic Oncology, Osaka Habikino Medical Center, Habikino, Japan

    Hidekazu Suzuki & Tomonori Hirashima

  8. Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan

    Masaki Kanazu & Nobuhiko Sawa

  9. Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan

    Junji Uchida

  10. Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan

    Mitsunori Morita

  11. Department of Respiratory Medicine, Itami City Hospital, Itami, Japan

    Takeshi Makio & Satoshi Hara

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  1. Hayato Kawachi
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Correspondence to Motohiro Tamiya.

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Conflict of interest

Drs. Kawachi, Fujimoto, Motohiro Tamiya, Akihiro Tamiya, Hirano, and Kumagai have received lecture fees from Taiho Pharmaceutical Co., Ltd. (Tokyo, Japan) and Merck Sharp & Dohme, Corp. (Tokyo, Japan). Drs. Yokoyama and Hirashima have received lecture fees from Taiho Pharmaceutical Co., Ltd. (Tokyo, Japan). Drs. Ishida and Kanazu have received lecture fees from Merck Sharp & Dohme, Corp. (Tokyo, Japan). All remaining authors have declared no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later aemndments or comparable ethical standards. The study protocol was approved by the review board of each of the 11 institutions and this study was registered with UMIN (University Hospital Medical Information Network in Japan reference number 000032470).

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Kawachi, H., Tamiya, M., Tamiya, A. et al. Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non–small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study. Invest New Drugs 38, 211–218 (2020). https://doi.org/10.1007/s10637-019-00882-5

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