As reported in The Lancet by Fizazi et al, the phase III PEACE-1 trial has shown that the addition of abiraterone and prednisone to androgen-deprivation therapy (ADT) and docetaxel improved radiographic progression-free survival and overall survival in patients with de novo metastatic castration-sensitive prostate cancer.
In the open-label 2 × 2 factorial design trial, 1,172 patients from sites in Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland were randomly assigned 1:1:1:1 between November 2013 and December 2018 to receive: standard of care consisting of ADT alone or with docetaxel at 75 mg/m² once every 3 weeks (n = 296); standard of care plus radiotherapy (n = 293); standard of care plus abiraterone at 1,000 mg once daily and prednisone at 5 mg twice daily (n = 292); or standard of care plus radiotherapy plus abiraterone (n = 291). The co-primary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was assessed first in the overall population and then in the population receiving ADT with docetaxel as standard of care.
Radiographic Progression-Free Survival and Overall Survival
Median follow-up was 3.5 years (interquartile range [IQR] = 2.8–4.6 years) for radiographic progression-free survival and 4.4 years (IQR = 3.5–5.4 years) for overall survival.
An adjusted Cox regression analysis showed no interaction between abiraterone and radiotherapy for radiographic progression-free survival (P = .64) or overall survival (P = .86), allowing pooled analysis of abiraterone efficacy. Among the 583 patients who received abiraterone, median radiographic progression-free survival was 4.46 years (IQR =1.72 years to not reached), compared with 2.22 years (IQR = 1.09–6.03 years) among 589 patients who did not receive abiraterone (hazard ratio [HR] = 0.54, 99.9% CI = 0.41–0.71, P < .0001). Median overall survival was 5.72 years (IQR = 2.72 years to not reached) among patients receiving abiraterone vs 4.72 years (IQR = 2.59 years to not reached) among those not receiving abiraterone (HR = 0.82, 95.1% CI = 0.69–0.98, P = .030). The number of deaths was 228 vs 268.
Among 355 patients who received abiraterone plus ADT with docetaxel, median radiographic progression-free survival was 4.46 years (IQR = 1.90 years to not reached), compared with 2.03 years (IQR = 1.09 years to not reached) among 355 who received ADT with docetaxel (HR = 0.50, 99.9% CI = 0.34–0.71, P < .0001). Median overall survival was not reached among patients receiving abiraterone vs 4.43 years (IQR = 2.47 years to not reached) among those not receiving abiraterone (HR = 0.75, 95.1% CI = 0.59–0.95, P = .017). The number of deaths was 121 vs 151.
In the total ADT with docetaxel population, grade ≥ 3 adverse events occurred in 217 (63%) of 347 patients who actually received abiraterone and 181 (52%) of 350 who received ADT with docetaxel, with the greatest differences observed in hypertension (22% vs 13%) and hepatotoxicity (6% vs 1%). Among other grade ≥ 3 adverse events, no differences were observed for neutropenia (10% vs 9%), febrile neutropenia (5% vs 5%), increased gamma-glutamyl transferase (5% vs 4%), increased alkaline phosphatase (4% vs 3%), erectile dysfunction (2% vs 1%), fatigue (3% vs 4%), or peripheral neuropathy (1% vs 2%). Fatal adverse events occurred in seven patients (2%) vs three patients (1%).
The investigators concluded: “Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients.”
Karim Fizazi, MD, Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Saclay, Villejuif, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Janssen-Cilag, Ipsen, Sanofi, and the French Government. For full disclosures of the study authors, visit www.thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.