Kazutaka Hosoya1, Daichi Fujimoto2, Takeshi Morimoto3, Toru Kumagai4, Akihiro Tamiya5, Yoshihiko Taniguchi5, Toshihide Yokoyama6, Tadashi Ishida6, Katsuya Hirano7, Hirotaka Matsumoto7, Ryota Kominami8, Keisuke Tomii1, Hidekazu Suzuki9, Tomonori Hirashima9, Junji Uchida10, Mitsunori Morita11, Masaki Kanazu12, Nobuhiko Sawa12, Takeshi Makio13, Satoshi Hara13, Motohiro Tamiya4. 1. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 2. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: daichi@kcho.jp. 3. Clinical Research Center, Kobe City Medical Center General Hospital, Kobe, Japan; Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan. 4. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. 5. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan. 6. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan. 7. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan. 8. Department of Respiratory Medicine, Himeji Medical Center, Himeji, Japan. 9. Department of Thoracic Oncology, Osaka Habikino Medical Center, Habikino, Osaka, Japan. 10. Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan. 11. Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan. 12. Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan. 13. Department of Respiratory Medicine, Itami City Hospital, Itami, Japan.
Abstract
INTRODUCTION: Previous studies have described an association between immune-related adverse events (irAEs) and better outcomes in patients administered nivolumab for advanced non-small-cell lung cancer. However, the patients in previous studies were not stratified by potential predictive factors, such as programmed cell death ligand 1 status and treatment lines. Additionally, little is known of whether the timing and type of irAEs can inform the prediction of outcomes. PATIENTS AND METHODS: We prospectively investigated the association between irAEs and outcomes in the single-center cohort that included patients administered nivolumab in the second or later line of therapy. Subsequently, we confirmed these findings in a retrospective multicenter cohort that included patients with programmed cell death ligand 1 tumor proportion score of ≥ 50% who had received first-line pembrolizumab. The primary outcome was progression-free survival (PFS). RESULTS: In the prospective cohort (n = 76), the median PFS was significantly longer for the patients experiencing irAEs within 2 weeks of beginning nivolumab compared with the PFS for those who did not (median, 5.0 months [95% confidence interval (CI), 2.1-8.6 months] vs. median, 2.0 months [95% CI, 1.9-2.5 months]; P = .046). The association was stronger with earlier (within 2 weeks) than with later (within 6 weeks) irAEs. In the retrospective cohort (n = 148), the median PFS was significantly longer for the patients with early irAEs (within 3 weeks) than for those without (median, not reached [95% CI, 5.9 months to not reached] vs. median, 6.9 months [95% CI, 4.2-9.7 months]; P = .04). Rash was common and a better predictor of outcomes in both cohorts. CONCLUSION: Our results have provided firmer evidence of the association between the occurrence of irAEs and outcomes and suggest that early irAEs (especially rash) might better predict outcomes.
INTRODUCTION: Previous studies have described an association between immune-related adverse events (irAEs) and better outcomes in patients administered nivolumab for advanced non-small-cell lung cancer. However, the patients in previous studies were not stratified by potential predictive factors, such as programmed cell death ligand 1 status and treatment lines. Additionally, little is known of whether the timing and type of irAEs can inform the prediction of outcomes. PATIENTS AND METHODS: We prospectively investigated the association between irAEs and outcomes in the single-center cohort that included patients administered nivolumab in the second or later line of therapy. Subsequently, we confirmed these findings in a retrospective multicenter cohort that included patients with programmed cell death ligand 1 tumor proportion score of ≥ 50% who had received first-line pembrolizumab. The primary outcome was progression-free survival (PFS). RESULTS: In the prospective cohort (n = 76), the median PFS was significantly longer for the patients experiencing irAEs within 2 weeks of beginning nivolumab compared with the PFS for those who did not (median, 5.0 months [95% confidence interval (CI), 2.1-8.6 months] vs. median, 2.0 months [95% CI, 1.9-2.5 months]; P = .046). The association was stronger with earlier (within 2 weeks) than with later (within 6 weeks) irAEs. In the retrospective cohort (n = 148), the median PFS was significantly longer for the patients with early irAEs (within 3 weeks) than for those without (median, not reached [95% CI, 5.9 months to not reached] vs. median, 6.9 months [95% CI, 4.2-9.7 months]; P = .04). Rash was common and a better predictor of outcomes in both cohorts. CONCLUSION: Our results have provided firmer evidence of the association between the occurrence of irAEs and outcomes and suggest that early irAEs (especially rash) might better predict outcomes.
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