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

Abstract

Background: This registrational trial evaluated the efficacy, safety, and patient-reported outcomes of axitinib versus sorafenib as a second-line treatment in Asian patients with clear-cell metastatic renal cell carcinoma (mRCC).

Methods: In this open-label, multicenter study, previously treated Asian patients with clear-cell mRCC were stratified by Eastern Cooperative Oncology Group performance status and prior therapy and randomized in a 2:1 ratio to receive axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). The primary end point was progression-free survival (PFS) assessed by a masked independent review committee.

Results: A total of 204 Asian patients received axitinib (n=135) or sorafenib (n=69). Median PFS (95% confidence interval [CI]) was 6.5 (4.7-9.1) months with axitinib versus 4.8 (3.0-6.5) months with sorafenib (hazard ratio, 0.731; 95% CI, 0.506-1.058; one-sided P=0.0531). The objective response rate (95% CI) was 23.7% (16.8%-31.8%) with axitinib versus 10.1% (4.2%-19.8%) with sorafenib. Common, 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%-24% 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.

Trial registration: ClinicalTrials.gov NCT00920816.

Keywords: axitinib; renal cell carcinoma; sorafenib; vascular endothelial growth factor receptor inhibitor.

Figures

Figure 1

CONSORT diagram. Abbreviations: AE, adverse event; ITT, intention-to-treat; CONSORT, Consolidated Standards of Reporting Trials.

Figure 2

Kaplan–Meier estimates of masked IRC-assessed PFS. Notes: (A) intention-to-treat population, (B) patients previously treated with sunitinib, and (C) patients previously treated with cytokines. *Stratified by ECOG PS (and for prior therapy, in panel a only); assuming proportional hazards, HR <1 indicates a reduction in favor of axitinib and HR >1 indicates a reduction in favor of sorafenib. Abbreviations: CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IRC, independent review committee; mPFS, median progression-free survival; PFS, progression-free survival.

Figure 3

Subgroup analysis of masked IRC-assessed progression-free survival with respect to baseline characteristics and prognostic factors. Notes: Analysis excluded three patients with ECOG PS 0 who had not received first-line systemic therapy and one patient with ECOG PS 2. 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.