Effectiveness and safety of second-line tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) for whom first-line immuno-oncology (I-O) combination therapy was discontinued because of adverse events (AEs) remain to be determined.
Clinicopathological data were retrospectively collected from 34 institutions between August 2018 and January 2022 for 243 patients with mRCC who received second-line TKIs after first-line I-O combination therapy. Two patients who requested discontinuation of first-line I-O combination therapy were excluded. Oncological outcomes and safety were compared between patients who discontinued first-line I-O combination therapy because of progressive disease (Group PD) and AEs (Group AE). First- and second-line overall survival (OS) were defined as the time from the start of first- and second-line therapy to death, respectively. Propensity score matching was applied to adjust prognostic factors between the 2 groups.
There were 179 patients in Group PD and 62 patients in Group AE. Objective response rate and disease control rate were similar between the 2 groups. Progression-free survival (PFS), second-line OS, and first-line OS were significantly longer in Group AE than in Group PD (median 13.6 months vs. 8.5 months, P = 0.005; median not reached [NR] vs. 19.5 months, P = .005; median NR vs. 30.8 months, P = .012, respectively). After propensity score matching, PFS and second-line OS were still significantly longer and first-line OS tended to be longer in Group AE than in Group PD. There were no significant differences in the occurrence of AEs of any grade, including severe grades of 3 or greater, between the 2 groups.
Second-line TKIs are safe and at least as effective in patients with mRCC who discontinued first-line I-O combination therapy because of AEs as they are in patients who discontinued because of PD.
Clinical genitourinary cancer. 2025 Feb 26 [Epub ahead of print]
Masayuki Takahashi, Yuto Matsushita, Takahiro Kojima, Takahiro Osawa, Tomokazu Sazuka, Shingo Hatakeyama, Keisuke Goto, Kazuyuki Numakura, Kazutoshi Yamana, Shuya Kandori, Kazutoshi Fujita, Kosuke Ueda, Hajime Tanaka, Ryotaro Tomida, Toshifumi Kurahashi, Yukari Bando, Takahiro Kimura, Naotaka Nishiyama, Shimpei Yamashita, Hisanori Taniguchi, Keisuke Monji, Ryo Ishiyama, Yoshihide Kawasaki, Takuma Kato, Shuichi Tatarano, Kimihiko Masui, Eijiro Nakamura, Tomoyuki Kaneko, Makito Miyake, Goshi Kitano, Takanobu Motoshima, Yusuke Shiraishi, Satoru Kira, Takaya Murashima, Hiroaki Hara, Masafumi Matsumura, Hiroshi Kitamura, Hideaki Miyake, Junya Furukawa, Japanese Urological Oncology Group
Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. Electronic address: ., Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan., Department of Urology, Aichi Cancer Center, Nagoya, Japan., Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan., Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan., Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan., Department of Urology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Department of Urology, Akita University Graduate School of Medicine, Akita, Japan., Department of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Department of Urology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan., Department of Urology, Kindai University Faculty of Medicine, Osakasayama, Japan., Department of Urology, Kurume University School of Medicine, Kurume, Japan., Department of Urology, Institute of Science Tokyo, Tokyo, Japan., Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan., Department of Urology, Hyogo Prefectural Cancer Center, Akashi, Japan., Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan., Department of Urology, Wakayama Medical University, Wakayama, Japan., Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan., Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Department of Urology, Tokyo Women's Medical University, Tokyo, Japan., Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan., Department of Urology, Faculty of Medicine, Kagawa University, Kita-gun, Japan., Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan., Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan., Department of Urology, National Cancer Center Hospital, Tokyo, Japan., Department of Urology, Teikyo University School of Medicine, Tokyo, Japan., Department of Urology, Nara Medical University, Nara, Japan., Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Department of Urology, Shizuoka General Hospital, Shizuoka, Japan., Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Japan., Department of Urology, Faculty of Medicine, Miyazaki University Hospital, Miyazaki, Japan., Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan., Department of Urology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.