title: 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.
abstract: OBJECTIVE
  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.
authors: Department of Urology, Yamagata University Faculty of Medicine, Yamagata.
authors: Yoshihiko
authors: Y
authors: Tomita
authors: Prostate Center and Division of Urology, Chiba Cancer Center, Chiba.
authors: Satoshi
authors: S
authors: Fukasawa
authors: Department of Urology, Keio University School of Medicine, Tokyo.
authors: Mototsugu
authors: M
authors: Oya
authors: Department of Urology, Kinki University School of Medicine, Osaka.
authors: Hirotsugu
authors: H
authors: Uemura
authors: Department of Urology, Hokkaido University Graduate School of Medicine, Hokkaido.
authors: Nobuo
authors: N
authors: Shinohara
authors: Department of Urology, Akita University School of Medicine, Akita, Japan.
authors: Tomonori
authors: T
authors: Habuchi
authors: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors: Brian I
authors: BI
authors: Rini
authors: Pfizer Oncology, San Diego, CA, USA.
authors: Ying
authors: Y
authors: Chen
authors: Pfizer Oncology, San Diego, CA, USA.
authors: Angel H
authors: AH
authors: Bair
authors: Department of Urology, Hamamatsu University School of Medicine, Shizuoka.
authors: Seiichiro
authors: S
authors: Ozono
authors: Department of Urology, Kyushu University, Graduate School of Medical Sciences, Fukuoka.
authors: Seiji
authors: S
authors: Naito
authors: Strategic Investigation on Comprehensive Cancer Network, Interfaculty Initiative in Information Studies/Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Tokyo, Japan.
authors: Hideyuki
authors: H
authors: Akaza
keywords: Japanese; axitinib; molecular targeted therapy; randomized clinical trial; renal cell carcinoma