Overall survival and final efficacy and safety results from a Japanese phase II study of axitinib in cytokine-refractory metastatic renal cell carcinoma

Abstract

In an open-label, multicenter phase II study of Japanese patients with cytokine-refractory metastatic renal cell carcinoma, axitinib showed substantial antitumor activity with an acceptable safety profile. Here, we report overall survival and updated efficacy and safety results. Sixty-four Japanese patients with metastatic renal cell carcinoma following prior therapy with cytokines were treated with axitinib at a starting dose of 5 mg b.i.d. Following median treatment duration of 14.2 months, median overall survival was 37.3 months (95% CI, 28.6-49.9). The objective response rate, the primary endpoint of the study, was 51.6% (95% CI, 38.7-64.2); the median duration of response, 11.1 months (95% CI, 8.2-13.7); and the median progression-free survival was 11.0 months (95% CI, 9.2-12.0), assessed by the independent review committee. Common treatment-related all-grade adverse events were hypertension (88%), hand-foot syndrome (75%), diarrhea (66%), proteinuria (63%), fatigue (55%) and dysphonia (53%). In an exploratory analysis, median overall survival was found to be significantly longer in patients who had greater decreases in plasma levels of soluble vascular endothelial growth factor receptor-2 during the first cycle of treatment. In conclusion, the present study showed axitinib to be effective, and toxicities with long-term treatment were generally controllable with axitinib dose modification and/or standard medications in these Japanese patients. Some frequently reported adverse events warrant close monitoring and management. Changes in the plasma levels of soluble vascular endothelial growth factor receptor-2 may be used as a prognostic factor for overall survival in metastatic renal cell carcinoma following axitinib treatment. This study is registered at ClinicalTrial.gov (identifier NCT00569946).

Keywords: Axitinib; Japanese; cytokine-refractory; overall survival; renal cell carcinoma.

© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Figures

Fig. 1

Kaplan–Meier estimates of (a) independent review committee-assessed progression-free survival and (b) overall survival. CI, confidence interval; OS, overall survival; PFS, progression-free survival.

Fig. 2

Kaplan–Meier estimates of overall survival by (a) MSKCC risk group and (b) baseline ECOG PS. CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; MSKCC, Memorial Sloan-Kettering Cancer Center; NE, not estimable; OS, overall survival.

Fig. 3

Kaplan–Meier estimates of overall survival by (a) maximum diastolic blood pressure from initiation of treatment to cycle 2 day 1 and (b) percent change in sVEGFR-2 from baseline to cycle 2 day 1. *Median % change = −33.5. CI, confidence interval; HR, hazard ratio; NE, not estimable; OS, overall survival; sVEGFR, soluble vascular endothelial growth factor receptor.