Shinobu Hosokawa1, Eiki Ichihara2, Daijiro Harada3, Shoichi Kuyama4, Koji Inoue5, Kenichi Gemba6, Hirohisa Ichikawa7, Yuka Kato8, Naohiro Oda9, Isao Oze10, Tomoki Tamura4, Toshiyuki Kozuki3, Takahiro Umeno1, Toshio Kubo11, Katsuyuki Hotta8, Akihiro Bessho1, Yoshinobu Maeda12, Katsuyuki Kiura13. 1. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan. 2. Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2-5-1 Shikata-cho Kita-ku, Okayama City, Okayama, 700-8558, Japan. ichiha-e@md.okayama-u.ac.jp. 3. Department of Thoracic Oncology, NHO Shikoku Cancer Center, Matsuyama, Japan. 4. Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Japan. 5. Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Japan. 6. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan. 7. Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, Japan. 8. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. 9. Department of Respiratory Medicine, Fukuyama City Hospital, Fukuyama, Japan. 10. Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. 11. Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan. 12. Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 13. Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2-5-1 Shikata-cho Kita-ku, Okayama City, Okayama, 700-8558, Japan.
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.
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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