In a meta-analysis of two STAMPEDE platform phase III trials reported in The Lancet, Gerhardt Attard, PhD, and colleagues found that the addition of abiraterone acetate and prednisolone with or without enzalutamide to androgen-deprivation therapy (ADT) was associated with improved metastasis-free survival in patients with high-risk nonmetastatic prostate cancer.
Study Details
The analysis included a total of 1,974 patients enrolled in the two open-label trials from sites in the United Kingdom and Switzerland between November 2011 and March 2016. In one trial, 914 patients were randomly assigned to receive ADT and abiraterone plus prednisolone (n = 459) or ADT alone (n = 455). In the second trial, 1,060 patients were randomly assigned to receive ADT plus abiraterone/prednisolone and enzalutamide (n = 527) or ADT alone (n = 533). Abiraterone was given at 1,000 mg/day, prednisolone at 5 mg/day, and enzalutamide at 160 mg/day. In the total analysis population, the combination groups included 986 patients and the control groups included 988 patients. Patients received combination therapy for up to 2 years and ADT was given for 3 years. The primary outcome measure was metastasis-free survival.
Key Findings
Median follow-up was 72 months (interquartile range [IQR] = 60–84 months).
Among men with high-risk nonmetastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population.— Gerhardt Attard, PhD, and colleagues
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Metastasis-free survival events occurred in 180 patients in the combination groups vs 306 in the control groups. Median metastasis-free survival was not reached (IQR = not evaluable–not evaluable) in the combination group vs not reached (IQR = 97 months–not evaluable) in the control group (hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.44–0.64, P < .0001). Rates at 6 years were 82% vs 69%. No evidence of difference was observed when enzalutamide and abiraterone were given together vs abiraterone alone (interaction HR = 1.02, 95% CI = 0.70–1.50, P = .91) and no evidence of between-trial heterogeneity was observed (I² P = .90).
Death occurred in 147 patients in the combination groups vs 236 in the control groups. Median overall survival was not reached (IQR = not evaluable–not evaluable) vs not reached (IQR = 103 months–not evaluable), with a hazard ratio of 0.60 (95% CI = 0.48–0.73, P < .0001). Rates at 6 years were 86% vs 77%.
Death due to prostate cancer occurred in 73 patients in the combination groups vs 142 in the control groups. Median prostate cancer–specific survival was not reached (IQR = not evaluable–not evaluable) vs not reached (IQR = not evaluable–not evaluable), with a hazard ratio of 0.49 (95% CI = 0.37–0.65, P < .0001). Rates at 6 years were 93% vs 85%.
Treatment failure events (including prostate-specific antigen progression) occurred in 204 patients in the combination groups vs 402 in the control groups. Median failure-free survival was not reached (IQR = not evaluable–not evaluable) vs 86 months (IQR = 83 months–not evaluable), with a hazard ratio of 0.39 (95% CI = 0.33–0.47, P < .0001).
Progression-free survival events occurred in 138 patients in the combination groups vs 277 in the control groups. Median progression-free-survival was not reached (IQR = not evaluable–not evaluable) vs not reached (IQR = 103 months–not evaluable), with a hazard ratio of 0.44 (95% CI = 0.36–0.54, P < .0001).
For the combination vs control groups, grade ≥ 3 adverse events during the first 24 months occurred in 37% vs 29% of patients in the abiraterone trial and in 58% vs 32% in the abiraterone/enzalutamide trial.
The investigators concluded, “Among men with high-risk nonmetastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population.”
Dr. Attard, of the Cancer Institute, University College London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas. For full disclosures of the study authors, visit thelancet.com.
