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Central nervous systemic efficacy of immune checkpoint inhibitors and concordance between intra/extracranial response in non-small cell lung cancer patients with brain metastasis

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Abstract

Purpose

Immune checkpoint inhibitors (ICIs) markedly improve the clinical outcomes of advanced non-small-cell lung cancer (NSCLC). However, the intracranial efficacy of ICI is not well elucidated, and previous studies showed discordant outcomes of ICI between intracranial and extracranial diseases. We aimed to evaluate the clinical outcomes and the intracranial and extracranial response of patients with NSCLC and brain metastasis who were treated with ICI in the real-world setting.

Methods

A total of 55 patients (median age, 63 years [range 42–80]; male, 78%) who had NSCLC with brain metastasis and treated with ICI monotherapy were retrospectively analyzed. We separately assessed the response rates of brain lesions and systemic lesions, and estimated the overall survival (OS) and progression-free survival (PFS).

Results

The median OS and overall PFS were 17.0 months (95% CI 10.3–25.6) and 3.19 months (95% CI 2.24–5.03), respectively. The intracranial objective response rate and disease control rate of ICI were 36 and 54%, respectively. Among the 44 patients who showed disease progression, only 32% (n = 14) showed concordant outcomes and 9 patients (20%) showed opposing discordant outcomes. Eight patients continued ICI with local brain therapy after intracranial progression, and their median extracranial PFS and OS were 15 months (95% CI 5.0—not assessed [NA]) and 23.8 months (95% CI 14.7—NA), respectively.

Conclusions

ICI monotherapy had a clinically meaningful intracranial efficacy in NSCLC patients with brain metastasis. Watchful waiting and close monitoring without local radiotherapy might be feasible in NSCLC patients with asymptomatic active brain metastasis.

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Data availability

The data sets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C1234).

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Author notes

  1. Sora Kang and Hyehyun Jeong contributed equally as co-first authors.

Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea

    Sora Kang, Hyehyun Jeong, Dae Ho Lee, Sang-We Kim, Jae Cheol Lee, Chang Min Choi & Shinkyo Yoon

  2. Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Ji Eun Park & Ho Sung Kim

  3. Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Young-Hoon Kim

  4. Division of hemato-oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, 35015, South Korea

    Sora Kang

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  1. Sora Kang
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Contributions

All authors contributed to the clinical data resources and curation. JEP and SY contributed to study conceptualization, project administration, and supervision. SK and HJ contributed to data analysis and interpretation, and written first draft of the manuscript. All authors were reviewed and edited on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shinkyo Yoon.

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Competing interests

Dae Ho Lee declares honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CJ Healthcare, ChongKunDang, Eli Lilly, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm and ST Cube. The other authors declare no competing interest.

Ethical approval

This study was reviewed and approved by the Institutional Review Board of Asan Medical center (approval number: 2021-1300, date of approval: August 25, 2021). The requirement of informed consent was waived due to the retrospective nature of the study.

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Kang, S., Jeong, H., Park, J.E. et al. Central nervous systemic efficacy of immune checkpoint inhibitors and concordance between intra/extracranial response in non-small cell lung cancer patients with brain metastasis. J Cancer Res Clin Oncol 149, 4523–4532 (2023). https://doi.org/10.1007/s00432-022-04251-3

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