Eiki Ichihara1, Daijiro Harada2, Koji Inoue3, Takuo Shibayama4, Shinobu Hosokawa5, Daizo Kishino6, Shingo Harita7, Nobuaki Ochi8, Naohiro Oda9, Naofumi Hara10, Katsuyuki Hotta11, Yoshinobu Maeda10, Katsuyuki Kiura12. 1. 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. 2. Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 3. Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Japan. 4. Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan. 5. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan. 6. Department of Respiratory Medicine, Himeji Red Cross Hospital, Himeji, Japan. 7. Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan. 8. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan. 9. Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan. 10. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 11. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. 12. Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan.
Abstract
OBJECTIVES: Immune checkpoint inhibitors (ICIs) are less effective in non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. However, a small percentage of patients with EGFR-mutant NSCLC do respond, and the characteristics of these patients are not known. Here, we identify the characteristics of patients who may respond to ICI therapy for EGFR-mutant NSCLC. PATIENTS AND METHODS: The medical records of NSCLC patients with EGFR mutations who received PD-1/PD-L1 antibody monotherapy at nine institutions were reviewed. RESULTS: In total, 58 patients with EGFR-mutant NSCLC were analyzed. Various clinical factors such as smoking history and EGFR mutation type were not associated with progression-free survival (PFS) of ICIs, while the PFS of prior EGFR tyrosine kinase inhibitors (TKIs) was inversely associated with that of ICIs. Patients who responded to prior EGFR TKIs for > 10 months exhibited a significantly shorter response to ICIs compared to those who had responded for ≤ 10 months (PFS of ICI: 1.6 vs. 1.9 months; hazard ratio: 2.54; 95% confidence interval 1.26-5.12; p = 0.009). However, patients who responded to ICIs for > 6 months responded to prior EGFR TKIs for significantly shorter periods compared to those who responded to ICIs for ≤ 6 months (PFS of prior EGFR TKI: 5.3 vs. 12.1 months; log-rank test: p = 0.0025). CONCLUSION: The duration of response to prior EGFR TKIs could be a predictive marker of ICI therapy in EGFR-mutant NSCLC patients.
OBJECTIVES: Immune checkpoint inhibitors (ICIs) are less effective in non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. However, a small percentage of patients with EGFR-mutant NSCLC do respond, and the characteristics of these patients are not known. Here, we identify the characteristics of patients who may respond to ICI therapy for EGFR-mutant NSCLC. PATIENTS AND METHODS: The medical records of NSCLCpatients with EGFR mutations who received PD-1/PD-L1 antibody monotherapy at nine institutions were reviewed. RESULTS: In total, 58 patients with EGFR-mutant NSCLC were analyzed. Various clinical factors such as smoking history and EGFR mutation type were not associated with progression-free survival (PFS) of ICIs, while the PFS of prior EGFR tyrosine kinase inhibitors (TKIs) was inversely associated with that of ICIs. Patients who responded to prior EGFR TKIs for > 10 months exhibited a significantly shorter response to ICIs compared to those who had responded for ≤ 10 months (PFS of ICI: 1.6 vs. 1.9 months; hazard ratio: 2.54; 95% confidence interval 1.26-5.12; p = 0.009). However, patients who responded to ICIs for > 6 months responded to prior EGFR TKIs for significantly shorter periods compared to those who responded to ICIs for ≤ 6 months (PFS of prior EGFR TKI: 5.3 vs. 12.1 months; log-rank test: p = 0.0025). CONCLUSION: The duration of response to prior EGFR TKIs could be a predictive marker of ICI therapy in EGFR-mutant NSCLCpatients.
Entities:
Keywords:
EGFR; Immune checkpoint inhibitor; Non-small-cell lung cancer
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