Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study

Yoshihiko Tomita; Satoshi Fukasawa; Mototsugu Oya; Hirotsugu Uemura; Nobuo Shinohara; Tomonori Habuchi; Brian I Rini; Ying Chen; Angel H Bair; Seiichiro Ozono; Seiji Naito; Hideyuki Akaza

doi:10.1093/jjco/hyw103

Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study

Jpn J Clin Oncol. 2016 Nov 1;46(11):1031-1041. doi: 10.1093/jjco/hyw103.

Authors

Affiliations

¹ Department of Urology, Yamagata University Faculty of Medicine, Yamagata.
² Prostate Center and Division of Urology, Chiba Cancer Center, Chiba.
³ Department of Urology, Keio University School of Medicine, Tokyo.
⁴ Department of Urology, Kinki University School of Medicine, Osaka.
⁵ Department of Urology, Hokkaido University Graduate School of Medicine, Hokkaido.
⁶ Department of Urology, Akita University School of Medicine, Akita, Japan.
⁷ Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
⁸ Pfizer Oncology, San Diego, CA, USA.
⁹ Department of Urology, Hamamatsu University School of Medicine, Shizuoka.
¹⁰ Department of Urology, Kyushu University, Graduate School of Medical Sciences, Fukuoka.
¹¹ Strategic Investigation on Comprehensive Cancer Network, Interfaculty Initiative in Information Studies/Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Tokyo, Japan.

Abstract

Objectives: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma.

Methods: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5 mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients.

Results: The objective response rate (95% confidence interval) was 66% (50-80%) vs. 44% (36-52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6-33.2) in an updated analysis. Hypertension, diarrhea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival.

Conclusions: Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation.

Keywords: Japanese; axitinib; molecular targeted therapy; randomized clinical trial; renal cell carcinoma.