Taigo Kato1,2, Akira Nagahara3, Norihiko Kawamura4, Wataru Nakata5, Tetsuji Soda6, Kyosuke Matsuzaki7, Koji Hatano8, Atsunari Kawashima8, Takeshi Ujike8, Ryoichi Imamura8, Kensaku Nishimura7, Shingo Takada6, Masao Tsujihata5, Seiji Yamaguchi4, Tetsuya Takao4, Kazuo Nishimura3, Norio Nonomura8, Motohide Uemura8,9. 1. Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. kato@uro.med.osaka-u.ac.jp. 2. Department of Urological Immuno-Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. kato@uro.med.osaka-u.ac.jp. 3. Department of Urology, Osaka International Cancer Institute, Chuo-ku, Osaka, 541-8567, Japan. 4. Department of Urology, Osaka General Medical Center, Sumiyoshi-ku, Osaka, 558-8558, Japan. 5. Departments of Urology, Osaka Rosai Hospital, Sakai, Osaka, 591-8025, Japan. 6. Department of Urology, Osaka Police Hospital, Tenoji-ku, Osaka, 543-0035, Japan. 7. Department of Urology, National Hospital Organization Osaka National Hospital, Chuo-ku, Osaka, 540-0006, Japan. 8. Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 9. Department of Urological Immuno-Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Abstract
BACKGROUND: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were correlated with favorable clinical outcome in patients with melanoma. However, in metastatic renal cell carcinoma (mRCC) patients, there have been few reports about the correlation between irAEs and clinical efficacy of anti-programmed cell death protein-1 (PD-1) therapy. METHODS: We retrospectively investigated 160 mRCC patients who started nivolumab monotherapy between September 2016 and July 2019. IrAEs were defined as patients' AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy. We compared the data of patients who received nivolumab into two groups based on the occurrence of irAEs and assessed clinical efficacy in both groups. RESULTS: Of all mRCC patients, 47 patients (29.4%) developed irAEs. In patients who developed irAEs, the objective response rate and disease control rate were 38.8% and 77.6%, which were significantly higher when compared to that in patients without irAEs (p = 0.012 and p < 0.001, respectively). Furthermore, the incidence of irAEs was significantly associated with an increase in progression-free survival (PFS) [Hazard ratio (HR) = 0.4867; p = 0.0006] and overall survival (OS) (HR = 0.526; p = 0.0252). Importantly, PFS and OS seemed to be similar in patients who discontinued treatment because of irAEs and in those who did not discontinue because of irAEs (p = 0.36 and p = 0.35, respectively). CONCLUSION: Development of irAEs strongly correlates with clinical benefit for mRCC patients receiving nivolumab monotherapy in real-world settings.
BACKGROUND: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were correlated with favorable clinical outcome in patients with melanoma. However, in metastatic renal cell carcinoma (mRCC) patients, there have been few reports about the correlation between irAEs and clinical efficacy of anti-programmed cell death protein-1 (PD-1) therapy. METHODS: We retrospectively investigated 160 mRCC patients who started nivolumab monotherapy between September 2016 and July 2019. IrAEs were defined as patients' AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy. We compared the data of patients who received nivolumab into two groups based on the occurrence of irAEs and assessed clinical efficacy in both groups. RESULTS: Of all mRCC patients, 47 patients (29.4%) developed irAEs. In patients who developed irAEs, the objective response rate and disease control rate were 38.8% and 77.6%, which were significantly higher when compared to that in patients without irAEs (p = 0.012 and p < 0.001, respectively). Furthermore, the incidence of irAEs was significantly associated with an increase in progression-free survival (PFS) [Hazard ratio (HR) = 0.4867; p = 0.0006] and overall survival (OS) (HR = 0.526; p = 0.0252). Importantly, PFS and OS seemed to be similar in patients who discontinued treatment because of irAEs and in those who did not discontinue because of irAEs (p = 0.36 and p = 0.35, respectively). CONCLUSION: Development of irAEs strongly correlates with clinical benefit for mRCC patients receiving nivolumab monotherapy in real-world settings.