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

ObjectiveAxitinib 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.MethodsA 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.ResultsTwenty-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.ConclusionsAxitinib 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.

Axitinib versus sorafenib as a second-line therapy in Asian patients with metastatic renal cell carcinoma: results from a randomized registrational study

“…Axitinib treatment resulted in numerically longer PFS and higher ORR in patients previously treated with cytokines than patients previously treated with sunitinib, which is consistent with the results from the global AXIS trial as well as the subgroup of patients from Japan 22,23. Cross-trial comparisons should be interpreted with caution because of potential methodologic and other differences.…”

“…The outcome for sorafenib in the current study was similar to that in a global Phase III trial of sorafenib that supported its use as a second-line treatment for advanced RCC 19,33. The results among Asian patients treated with axitinib in the current study are also similar to those observed in the global Phase III AXIS trial22 and the Asian subgroup of Japanese patients 23. The current study provides further evidence for the use of axitinib as a standard treatment in Asian patients with mRCC after the failure of a first-line systemic therapy.…”

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

“…Efficacy and safety of axitinib in Japanese patients with previously treated mRCC has been evaluated in a limited number of clinical studies (6,7), warranting additional investigation. The aim of the current analysis was to assess the efficacy and safety of axitinib in Japanese vs. non-Japanese patients with first-line mRCC (5).…”

Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial

“…In studies assessing sunitinib in patients with advanced renal-cell carcinoma (RCC), Korean and Japanese investigators independently reported that patients in their countries showed clinical efficacy that was at least as good as that seen in global studies, while incidences of hematologic AEs were higher than those observed in Western patients [13,14]. Similarly, analysis of a study comparing axitinib and sorafenib in patients with metastatic RCC showed a higher incidence of some AEs in Japanese patients than in the overall study population [15]. Although analysis of the overall GRID study population showed no significant variation in the efficacy of regorafenib across geographic regions, variations in the tolerability profile of regorafenib between populations have not been assessed [10].…”