Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized Phase 3 AXIS trial

Abstract

Objective: Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated.

Methods: A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma.

Results: Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8-6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130-1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand-foot syndrome (64%) and diarrhea (56%) for axitinib, and hand-foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand-foot syndrome, hypothyroidism and stomatitis.

Conclusions: Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.

Trial registration: ClinicalTrials.gov NCT00678392.

Keywords: axitinib; clinical trial; phase III; renal cell carcinoma; vascular endothelial growth factor receptors.

Figures

Figure 1.

Kaplan–Meier plot of progression-free survival assessed by Independent Review Committee (IRC) in (A) the overall population and (B) Japanese patients [(A) was reprinted from Rini et al. (15), Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial, p 1931–9, Copyright 2011, with permission from Elsevier. All rights reserved]. P values based on one-sided log-rank test stratified by ECOG performance status and prior therapy. CI, confidence interval; HR, hazard ratio; NE, not estimable; PFS, progression-free survival.

Figure 2.

IRC assessed maximum percent change in target lesions in Japanese patients treated with (A) axitinib (n = 24; 1 indeterminate) and (B) sorafenib (n = 25; 4 indeterminate). Dotted lines represent 30% decrease in target lesions.

Figure 3.

Objective response rate assessed by IRC. P values based on one-sided Cochran–Mantel–Haenszel test stratified by ECOG performance status and prior therapy.

Figure 4.

Kaplan–Meier analysis of time to deterioration (TTD) composite endpoint in Japanese patients. Composite endpoint of TTD was defined as time between the date of randomization to date of first occurrence of progression of disease, death or deterioration of symptoms, as measured by (A) FKSI-15 and (B) FKSI-DRS. P values based on one-sided log-rank test.