ECOG PS and prior therapy obtained from case report forms. Abbreviations: CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; IRC, independent review committee; MSKCC, Memorial Sloan Kettering Cancer Center; NA, not applicable. Based on masked IRC assessment, confirmed ORR was 23.7% with axitinib versus 10.1% with sorafenib ( em P /em =0.009; Table 2). grade 3, all-causality adverse events were hypertension (19.3%), weight decrease (5.2%), and proteinuria (5.2%) with axitinib and hypertension (8.7%) and palmar-plantar erythrodysesthesia (7.2%) with sorafenib. In a time-to-deterioration composite end point of death, progression, and worsening of Functional Assessment of Cancer Therapy Kidney Symptom Index score, patients treated with axitinib demonstrated a 17%C24% risk reduction compared with sorafenib-treated patients. Conclusion Axitinib is clinically active and well tolerated in previously treated Asian patients with mRCC, consistent with the results from the global Phase III trial. These results establish axitinib as a second-line treatment option for Asian patients with mRCC. strong class=”kwd-title” Keywords: axitinib, renal cell carcinoma, sorafenib, vascular endothelial growth factor receptor inhibitor Introduction In 2012, Droxidopa kidney cancer was diagnosed in more than 66,000 people in China and resulted in more than 25,000 deaths, a twofold increase in the number of deaths from 2008.1,2 Renal cell carcinoma (RCC) accounts for ~90% of kidney cancers, of which clear-cell carcinoma is the predominant histological subtype, accounting for 85% of RCC.3 In many countries, the management of metastatic RCC (mRCC) has changed dramatically with the introduction of molecularly targeted agents such as sunitinib,4C7 pazopanib,8C10 sorafenib,11C14 temsirolimus,15 and everolimus.16 However, according to the resource-stratified guidelines developed at the 2012 Asian Oncology Summit,17 interferon is still commonly used in Japan and considered the most cost-effective treatment in China.18 The availability of Asian-specific safety and efficacy data from a randomized clinical trial comparing one targeted agent versus another is obviously an important factor for making the decision to use a targeted agent in Asian populations. However, most of the available Asian-specific data come from single-arm Phase II, expanded access, or Droxidopa retrospective clinical studies.4C7,11C16,19 Axitinib, a Droxidopa potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3,20 is approved in the United States (Inlyta?; Pfizer Inc, New York, NY, USA21), European Union, Japan, Korea, and other countries for the treatment of advanced RCC after failure Droxidopa of prior systemic therapy. In the global Phase III AXIS trial, axitinib improved progression-free survival (PFS) compared with sorafenib in patients with mRCC (N=723) after failure of one prior systemic therapy.22 Median PFS was 6.7 months with axitinib versus 4.7 months with sorafenib Rabbit polyclonal to ACTR5 (hazard ratio [HR], 0.665; 95% confidence interval [CI], 0.544C0.812; one-sided em P /em 0.0001). In a subgroup analysis of patients from Japan enrolled in AXIS,23 axitinib resulted in longer PFS and higher objective response rate (ORR) compared with sorafenib, consistent with the results obtained in the overall population.22 The nature and incidence of adverse events (AEs) observed in Japanese patients were generally similar to those reported in the overall population; however, AEs more frequently reported by Japanese patients treated with axitinib included hypertension and hypothyroidism. Furthermore, treatment with axitinib had a statistically significant advantage Droxidopa compared with sorafenib on the composite end point of time-to-treatment deterioration, defined as death, disease progression, or worsening of symptoms (based on the Functional Assessment of Cancer Therapy Kidney Symptom Index [FKSI] questionnaire and FKSIC Disease-Related Symptoms [FKSI-DRS]).22 The time-to-deterioration FKSI-15 composite end point showed a 17% reduction in risk for axitinib versus sorafenib (HR, 0.829; 95% CI, 0.701C0.981; one-sided em P /em =0.014) and the time-to-deterioration FKSI-DRS composite end point showed a 16% risk reduction for axitinib versus sorafenib (HR, 0.838; 95% CI, 0.707C0.993; one-sided em P /em =0.0203).22 An ongoing study in previously treated Asian patients with advanced RCC was designed to support the registration of axitinib in China and to satisfy regulatory requirements in that country. As such, the study has a similar design to the previous Phase III AXIS trial in which patients with advanced RCC were treated with axitinib following failure of one prior systemic first-line regimen.22 Based on Phase I studies that showed comparable axitinib pharmacokinetics between white and Japanese24,25 or Chinese26 populations, axitinib dosage used in this Asian population was similar to that used in the predominantly white population in the.