Cabozantinib in advanced renal cell carcinoma: A phase II, open-label, single-arm study of Japanese patients

Yoshihiko Tomita, Katsunori Tatsugami, Noboru Nakaigawa, Takahiro Osawa, Mototsugu Oya, Hiroomi Kanayama, Chihiro Nakayama Kondoh, Naoto Sassa, Kazuo Nishimura, Masahiro Nozawa, Naoya Masumori, Yasuhide Miyoshi, Shingo Kuroda, Shingo Tanaka, Akiko Kimura, Satoshi Tamada, Yoshihiko Tomita, Katsunori Tatsugami, Noboru Nakaigawa, Takahiro Osawa, Mototsugu Oya, Hiroomi Kanayama, Chihiro Nakayama Kondoh, Naoto Sassa, Kazuo Nishimura, Masahiro Nozawa, Naoya Masumori, Yasuhide Miyoshi, Shingo Kuroda, Shingo Tanaka, Akiko Kimura, Satoshi Tamada

Abstract

Objectives: To evaluate the efficacy and safety of cabozantinib, through a bridging study to METEOR, in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.

Methods: This phase II, open-label, single-arm study (ClinicalTrials.gov registration number: NCT03339219) included adult Japanese patients with advanced renal cell carcinoma and measurable disease who had received one or more tyrosine kinase inhibitors. Patients received cabozantinib 60 mg orally once daily while there was clinical benefit, or until unacceptable toxicity or disease progression. The primary end-point was objective response rate per Response Evaluation Criteria in Solid Tumors Version 1.1. Secondary end-points included clinical benefit rate (complete or partial response, or ≥8-week stable disease), progression-free survival, overall survival and safety.

Results: Of the 35 patients enrolled, 68.6%, 22.9% and 8.6% had previously received one, two and three prior tyrosine kinase inhibitors, respectively. The median duration of cabozantinib exposure was 27.0 weeks (range 5.1-43.0 weeks). The objective response rate was 20.0% (90% confidence interval 9.8-34.3%), and the clinical benefit rate was 85.7% (95% confidence interval 69.7-95.2%). The 6-month estimated progression-free survival was 72.3% (95% confidence interval 53.3-84.6%); the median progression-free survival and overall survival were not reached. All patients reported adverse events, which were manageable by supportive treatment or dose modification; two patients (5.7%) discontinued therapy due to adverse events.

Conclusions: The results showed that findings from METEOR can be extrapolated, and that cabozantinib 60 mg/day is a viable treatment option in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.

Keywords: Japan; cabozantinib; receptor tyrosine kinase; renal cell carcinoma; tyrosine kinase inhibitor.

Conflict of interest statement

Yoshihiko Tomita received honoraria from Astellas Medivation, Bristol‐Myers Squibb, Novartis, Ono Pharmaceutical and Pfizer; consulting fees from Novartis, Ono Pharmaceutical and Taiho Pharmaceutical; and grants or funds from Takeda Pharmaceutical, Astellas Medivation, AstraZeneca, Ono Pharmaceutical, Pfizer and Chugai Pharmaceutical. Katsunori Tatsugami received lecture fees from Ono Pharmaceutical and Bristol‐Myers Squibb. Noboru Nakaigawa, Takahiro Osawa, Naoto Sassa and Yasuhide Miyoshi have no potential conflicts to report. Mototsugu Oya received honoraria from Pfizer, Novartis, Bayer, Ono Pharmaceutical and Bristol‐Myers Squibb; consulting fees from Bayer; and grants or funds from Pfizer and Novartis. Hiroomi Kanayama received consulting fees from Takeda Pharmaceutical; grants or funds from Takeda Pharmaceutical, Astellas Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, Pfizer, MSD, Sanofi and Nihon Medi‐Physics; and lecture fees from Takeda Pharmaceutical, Astellas Pharmaceutical, Pfizer, Bayer, Ono Pharmaceutical, Janssen Pharmaceutical and MSD. Chihiro Nakayama Kondoh received honoraria from Takeda Pharmaceutical, Chugai Pharmaceutical, Bristol‐Myers Squibb, MSD and Eisai Company. Kazuo Nishimura received honoraria from Astellas Pharmaceutical and Novartis; consulting fees from Astellas Pharmaceutical, AstraZeneca and Janssen Pharmaceutical; and grants or funds from Bayer. Masahiro Nozawa received lecture fees from Bristol‐Myers Squibb, Ono Pharmaceutical and Novartis. Naoya Masumori received honoraria from Takeda Pharmaceutical, and grants or funds from Ono Pharmaceutical and Takeda Pharmaceutical. Shingo Kuroda and Akiko Kimura are employees of Takeda Pharmaceutical. Shingo Tanaka worked with Takeda Pharmaceutical as a contracted employee of a CRO to support their drug development. Satoshi Tamada received fees for lectures, and advisory boards from Bayer, Bristol‐Myers Squibb, MSD, Novartis, Ono Pharmaceutical, Pfizer and Takeda Pharmaceutical.

© 2020 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

Figures

Fig. 1
Fig. 1
Waterfall plot of the best percentage change in the target lesion size (full analysis set). Change in the target lesion calculated by the sum of product diameters. Two patients with no target lesions and one participant with no post‐baseline tumor assessment results were excluded.
Fig. 2
Fig. 2
Kaplan–Meier plot of PFS per RECIST 1.1 (full analysis set).
Fig. 3
Fig. 3
Kaplan–Meier plot of OS (full analysis set).

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