Abstract
Background
The role of pembrolizumab in the treatment of poor performance status (PS) patients remains unclear.
Patients and methods
We conducted a phase II trial to investigate the efficacy and safety of pembrolizumab as first-line therapy for non-small-cell lung cancer (NSCLC) patients with PSs of 2–3 and programmed cell death ligand 1 (PD-L1) expression ≥ 50%. The primary endpoint of this study was the objective response rate (ORR).
Results
Fourteen patients treated at eight institutions were enrolled. Most patients had PS 2 (12/14; 86%) and others had PS 3 (2/14; 14%). The ORR was 57.1% (95% confidence interval 28.9–82.3%), which met the primary endpoint. The median progression-free survival (PFS) and 1-year PFS rates were 5.8 months and 20.0%, respectively. At the time of data cut-off, one patient had received treatment for more than 1 year; another patient had received treatment for more than 2 years. Nine patients had improved PS with treatment (Wilcoxon signed-rank test, p = 0.003). Two patients had immune-related adverse events ≥ grade 3: grades 5 and 3 elevation in alanine and aspartate aminotransferases. Two PS 3-stage patients were diagnosed with clinically progressive disease prior to initial computed tomography; both died within 2 months.
Conclusion
Pembrolizumab was effective for the treatment of NSCLC patients with a poor PS and PD-L1 level ≥ 50%. However, given the poor outcomes of the PS 3 patients, the drug is not indicated for such patients. Adverse events, including liver dysfunction, should be carefully monitored.
Registration ID
UMIN000030955.
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Data availability
The datasets generated and/or analyzed in this report are available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank Masafumi Fujii of the Kawasaki College of Allied Health Professions (a member of the Safety Review Committee). We also thank all investigators at the participating institutions. All authors contributed to study coordination among the various hospitals. We received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.
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E. Ichihara has received honoraria from Eli Lilly Japanand research funds from MSD, Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Janssen Pharmaceutical K.K. T. Kubo has received honoraria from Chugai Pharmaceutical Co. Ltd. T. Kozuki has received honoraria from AstraZeneca, Eli Lilly Japan, and Ono Pharmaceutical Co. Ltd., and research funds from MSD, Chugai Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd and Merck. S. Kuyama has received honoraria from Chugai Pharmaceutical Co. Ltd. K. Hotta received honoraria from Pfizer, AZ, Chugai, Lilly, Takeda, MSD, BMS, Ono, Taiho, and Boehringer-Ingelheim, and research funds from MSD, AZ, Chugai, Lilly, BMS, and Abbvie outside the submitted work. A. Bessho has received research funds from Ono Pharmaceutical Co. Ltd., AstraZeneca, MSD, and Chugai Pharmaceutical CO. Ltd. Y. Maeda has received honoraria from Novartis and research funds from Otsuka Pharmaceutical Co. Ltd., Eisai, MSD, Asahi Kasei Pharma, Chugai Pharmaceutical Co. Ltd., Nippon Shinyaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Kyowa Kirin, Astellas, Novartis, AstraZeneca, Janssen Pharmaceutical K.K., and Mundipharma K.K. K. Kiura has received honoraria from MSD and research funds from Nippon Kayaku Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Bristol Myers Squibb, Takeda Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Shionogi Pharmaceutical Co. Ltd., Boehringer Ingelheim, and MSD.
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Hosokawa, S., Ichihara, E., Harada, D. et al. Pembrolizumab in advanced NSCLC patients with poor performance status and high PD-L1 expression: OLCSG 1801. Int J Clin Oncol 27, 1139–1144 (2022). https://doi.org/10.1007/s10147-022-02164-2
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DOI: https://doi.org/10.1007/s10147-022-02164-2