Ryo Morita1, Kyoichi Okishio2, Junichi Shimizu3, Haruhiro Saito4, Hiroshi Sakai5, Young Hak Kim6, Osamu Hataji7, Makiko Yomota8, Makoto Nishio9, Keisuke Aoe10, Osamu Kanai11, Toru Kumagai12, Kayoko Kibata13, Hiroaki Tsukamoto14, Satoshi Oizumi15, Daichi Fujimoto16, Hiroshi Tanaka17, Keiko Mizuno18, Takeshi Masuda19, Toshiyuki Kozuki20, Takashi Haku21, Hiroyuki Suzuki22, Isamu Okamoto23, Hirotoshi Hoshiyama24, Junya Ueda25, Yuichiro Ohe26. 1. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: rmorita0204@gmail.com. 2. Department of Thoracic Oncology, National Hospital Organization Kinki - Chuo Chest Medical Center, Osaka, Japan. 3. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan. 4. Department of Thoracic Oncology, Kanagawa Cancer Center, Kanagawa, Japan. 5. Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan. 6. Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan. 7. Department of Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan. 8. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 9. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 10. Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Yamaguchi, Japan. 11. Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan. 12. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. 13. Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan. 14. Department of Respiratory Medicine, National Hospital Organization Himeji Medical Center, Hyogo, Japan. 15. Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Hokkaido, Japan. 16. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan. 17. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 18. Department of Pulmonary Medicine, Kagoshima University Hospital, Kagoshima, Japan. 19. Department of Respiratory Internal Medicine, Hiroshima University Hospital, Hiroshima, Japan. 20. Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Ehime, Japan. 21. Respiratory Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan. 22. Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan. 23. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 24. Bristol-Myers Squibb K.K., Tokyo, Japan. 25. Ono Pharmaceutical Co., Ltd, Osaka, Japan. 26. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Abstract
OBJECTIVES: To describe the treatment patterns and determine the effectiveness and safety of nivolumab treatment for non-small cell lung cancer (NSCLC) in real-world setting in Japan. MATERIALS AND METHODS: Japanese patients with NSCLC who received nivolumab were analyzed retrospectively. Patients who had started nivolumab treatment between April 2016 and December 2016 were enrolled. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness and safety of nivolumab treatment and that of treatments just before and after nivolumab treatment, and programmed death-ligand 1 (PD-L1) expression status, if available, were collected. Factors associated with nivolumab effectiveness identified by univariate and multivariate analyses were further investigated for plotting Kaplan-Meier curves of epidermal growth factor receptor (EGFR) gene mutation status, PD-L1 expression status, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: In this study, 901 NSCLC patients were enrolled. Nivolumab was used the most as a second line treatment with a median number of nivolumab doses of five. The median overall survival (OS) was 14.6 months, one-year survival rate was 54.3 %, and median progression-free survival (PFS) was 2.1 months. The objective response rate was 20.5 % and disease control rate was 57.4 %. According to multivariate analyses, better OS and PFS were associated with favorable ECOG PS and absence of liver metastasis. Better PFS was observed in patients without EGFR mutation and patients with smoking history. PFS and best overall response in PD-L1 expression subgroups were expression level-dependent. The overall incidence of irAEs was 45.8 %, and the incidence of adverse events of grade 3 or higher was 14.0 %. CONCLUSION: The real-world effectiveness and safety of nivolumab is consistent with that reported by previous clinical trials and other real-world data. Subgroup analysis showed that ECOG PS, EGFR mutation status, smoking status, and PD-L1 were associated with the effectiveness of nivolumab.
OBJECTIVES: To describe the treatment patterns and determine the effectiveness and safety of nivolumab treatment for non-small cell lung cancer (NSCLC) in real-world setting in Japan. MATERIALS AND METHODS: Japanese patients with NSCLC who received nivolumab were analyzed retrospectively. Patients who had started nivolumab treatment between April 2016 and December 2016 were enrolled. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness and safety of nivolumab treatment and that of treatments just before and after nivolumab treatment, and programmed death-ligand 1 (PD-L1) expression status, if available, were collected. Factors associated with nivolumab effectiveness identified by univariate and multivariate analyses were further investigated for plotting Kaplan-Meier curves of epidermal growth factor receptor (EGFR) gene mutation status, PD-L1 expression status, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: In this study, 901 NSCLCpatients were enrolled. Nivolumab was used the most as a second line treatment with a median number of nivolumab doses of five. The median overall survival (OS) was 14.6 months, one-year survival rate was 54.3 %, and median progression-free survival (PFS) was 2.1 months. The objective response rate was 20.5 % and disease control rate was 57.4 %. According to multivariate analyses, better OS and PFS were associated with favorable ECOG PS and absence of liver metastasis. Better PFS was observed in patients without EGFR mutation and patients with smoking history. PFS and best overall response in PD-L1 expression subgroups were expression level-dependent. The overall incidence of irAEs was 45.8 %, and the incidence of adverse events of grade 3 or higher was 14.0 %. CONCLUSION: The real-world effectiveness and safety of nivolumab is consistent with that reported by previous clinical trials and other real-world data. Subgroup analysis showed that ECOG PS, EGFR mutation status, smoking status, and PD-L1 were associated with the effectiveness of nivolumab.