An Indirect Comparison of Everolimus Versus Axitinib in US Patients With Advanced Renal Cell Carcinoma in Whom Prior Sunitinib Therapy Failed.

Abstract

PURPOSE:

The purpose of this study was to perform a weight-adjusted indirect comparison to approximate the relative efficacy of everolimus versus axitinib among patients with second-line metastatic renal cell carcinoma in whom sunitinib therapy previously failed.

METHODS:

Individual patient data from the RECORD-1 (Renal Cell Cancer Treatment With Oral RAD001 Given Daily) Phase III clinical trial provided information for patients taking everolimus. Summary baseline clinical and demographic characteristics and progression-free survival (PFS) outcomes were available for patients taking axitinib who were included in the AXIS (axitinib versus sorafenib) Phase III clinical trial. A Bayesian latent class mixture model differentiating responders and nonresponders and with imbedded Weibull regression on PFS was used to identify sex, Memorial Sloan-Kettering Cancer Center risk score, and time receiving prior sunitinib therapy as prognostic factors for PFS based on posterior probability >95%. Patients taking everolimus were weighted up or down based on their combination of prognostic variables. Weights were calculated by dividing the proportion of patients observed in AXIS for a given characteristic by the proportion observed in RECORD-1 and taking the product of the values derived for all three weighting variables considered. Weighted PFS distributions were derived with bootstrapped 95% CIs and compared with those reported for the AXIS trial.

FINDINGS:

After weighting, distributions of the 3 key baseline characteristics were more closely aligned between the 2 studies; however, some differences remained. A slightly lower rate of poor-risk patients was evident in RECORD-1 (30%) versus AXIS (36%), and a 9% lower proportion of males was observed in the everolimus group compared with the axitinib group. Distributions of time receiving prior sunitinib therapy were almost equivalent between the treatment arms. A median PFS of 4.7 months (95% CI, 3.5-10.6 months) was observed for patients in the weighted everolimus group compared with 4.8 months (95% CI, 4.5-6.4 months) in the AXIS trial.

IMPLICATIONS:

Similar median PFS point estimates and overlapping CIs suggest that everolimus and axitinib have similar efficacy. Although these results do not negate the need for direct comparison, this study may be used to inform clinical and reimbursement decisions until such evidence is available.

• Authors: Steven Sherman, Billy Amzal, Emiliano Calvo, Xufang Wang, Jinhee Park, Zhimei Liu, Chinjune Lin, Roman Casciano
• Journal: Clinical therapeutics (Clin Ther) (Oct 22 2015) ISSN: 1879-114X [Electronic] United States
• PMID: 26602976 (Publication Type: Journal Article)
• Copyright: Copyright © 2015. Published by Elsevier Inc.