Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment.
Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses.
In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1-131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1-40.6). Kaplan-Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4-18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6-85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline.
Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.
International journal of clinical oncology. 2023 Jan 03 [Epub ahead of print]
Noboru Nakaigawa, Yoshihiko Tomita, Satoshi Tamada, Katsunori Tatsugami, Takahiro Osawa, Mototsugu Oya, Hiroomi Kanayama, Yuji Miura, Naoto Sassa, Kazuo Nishimura, Masahiro Nozawa, Naoya Masumori, Yasuhide Miyoshi, Shingo Kuroda, Akiko Kimura
Department of Urology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan., Department of Urology, Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata, 951-8510, Japan., Department of Urology, Bell Land General Hospital, 500-3 Higashiyama, Naka-Ku, Sakai City, Osaka, 599-8247, Japan., Department of Urology, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokurakita-Ku, Kitakyushu, 802-8561, Japan., Department of Renal and Genitourinary Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan., Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan., Department of Urology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan., Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan., Department of Urology, Aichi Medical University School of Medicine, Yazako-Karimata 1-1, Nagakute, Aichi, 480-1195, Japan., Department of Urology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan., Department of Urology, Kindai University Faculty of Medicine, 377-2 Onohigashi, Osakasayama-Shi, Osaka-Fu, 589-0014, Japan., Department of Urology, Sapporo Medical University School of Medicine, S1 W16, Chuo-Ku, Sapporo, 060-8543, Japan., Department of Urology and Renal Transplantation, Yokohama City University Medical Center, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 326-0004, Japan., Statistical and Quantitative Sciences, Data Science Institute, Research and Development, Takeda Pharmaceutical Company Limited, 1-1 Doshomachi 4-Chome, Chuo-Ku, Osaka, 540-8645, Japan., Oncology Therapeutic Area Unit for Japan and Asia, Takeda Pharmaceutical Company Limited, 1-1 Doshomachi 4-Chome, Chuo-Ku, Osaka, 540-8645, Japan. .