Indirect comparison of abiraterone acetate and docetaxel for treatment of metastatic “hormone-sensitive” prostate cancer

Abstract

Background: Androgen deprivation therapy (ADT) with or without chemotherapy (docetaxel [DOC]) is recommended in the clinical guidelines as the mainstay of management for metastatic “hormone-sensitive” prostate cancer (mHSPC). The LATITUDE trial demonstrated the efficacy of abiraterone acetate in combination with prednisone and ADT (ADT+AA+P) vs ADT in newly diagnosed mHSPC pts with high-risk disease (NDx HRD). We performed an indirect comparison to determine the relative efficacy of AA vs DOC in mHSPC. Methods: We conducted a systematic literature review of randomized controlled trials (RCTs) of treatments for mHSPC. To increase comparability of results across studies, the population of interest from LATITUDE and DOC studies was restricted to men with NDx HRD and/or high volume disease (NDx HVD). Two RCTs (CHAARTED, GETUG-AFU 15), both evaluating ADT vs DOC+ADT, met the inclusion criteria. Fixed effects Bayesian network meta-analyses (NMAs) were performed to estimate the relative treatment effects for ADT+AA+P vs DOC+ADT on overall survival (OS) and radiographic progression-free survival (rPFS). The HVD subgroup of LATITUDE was used in the main analysis. The LATITUDE ITT population (NDx HRD) was included as a sensitivity analysis. As STAMPEDE did not report an NDx HVD/HRD subgroup, its M1 population was included in a sensitivity analysis. Results: The results for HRD/HVD suggested improvement with ADT+AA+P vs DOC+ADT in OS (HR 0.84) and in rPFS (HR 0.73), with Bayesian probabilities (P) for ADT+AA+P 86.8% (OS) and 99.2% (rPFS) more effective. Main results were consistent with all sensitivity analysis results (Table). Conclusions: Our analyses suggest that ADT+AA+P has greater reduction in risk of progression and death vs ADT+DOC. In absence of head-to-head trials, indirect comparisons based on BayesianNMA can provide useful insights to clinicians and reimbursement decision makers on the relative efficacy of treatment options for men with mHSPC. (Table presented).