Daichi Fujimoto1, Satoru Miura2, Kenichi Yoshimura3, Kazushige Wakuda4, Yuko Oya5, Toshihide Yokoyama6, Takashi Yokoi7, Tetsuhiko Asao8, Motohiro Tamiya9, Atsushi Nakamura10, Hiroshige Yoshioka11, Koji Haratani12, Shunsuke Teraoka13, Takaaki Tokito14, Shuji Murakami15, Akihiro Tamiya16, Shoichi Itoh17, Hiroshi Yokouchi18, Satoshi Watanabe19, Ou Yamaguchi20, Keisuke Tomii21, Nobuyuki Yamamoto13. 1. Internal Medicine III, Wakayama Medical University, Wakayama, 641-8509, Japan; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 2. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. Electronic address: miusat1118@niigata-cc.jp. 3. Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan. 4. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 5. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 6. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan. 7. Department of Respiratory Medicine and Hematology, Hyogo College of Medicine, Hyogo, Japan. 8. Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, Tokyo, Japan. 9. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. 10. Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan. 11. Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan. 12. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan. 13. Internal Medicine III, Wakayama Medical University, Wakayama, 641-8509, Japan. 14. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. 15. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 16. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan. 17. Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan. 18. Department of Respiratory Medicine, National Hospital Organization, Hokkaido Cancer Center, Sapporo, Japan. 19. Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 20. Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. 21. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Abstract
INTRODUCTION: Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. METHODS: We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. RESULTS: The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P = 0.03). CONCLUSIONS: Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. TRIAL REGISTRATION NUMBER: UMIN000038084.
INTRODUCTION: Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. METHODS: We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. RESULTS: The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P = 0.03). CONCLUSIONS: Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. TRIAL REGISTRATION NUMBER: UMIN000038084.