Combining androgen deprivation therapy (ADT), docetaxel, and abiraterone plus prednisone in patients with de novo metastatic castration-sensitive prostate cancer improved coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) with a modest increase in side effects, mostly hypertension, according to findings from the PEACE-1 study. The results from this open-label, randomised, phase III study with a 2 × 2 factorial design were reported by Prof. Karim Fizazi of the Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Saclay in Villejuif, France and study colleagues on 8 April 2022 in the Lancet.
The authors wrote in the study background that the current standard of care for patients with metastatic castration-sensitive prostate cancer supplements ADT with either docetaxel, second-generation hormonal therapy, or radiotherapy. They aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.
The ongoing PEACE-1 study is conducted at 77 hospitals in Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients are men, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an ECOG performance status of 0 and 1 or 2 due to bone pain.
Patients are randomly assigned (1:1:1:1) to standard of care comprising of ADT alone or with docetaxel, standard of care plus radiotherapy, standard of care plus abiraterone and prednisone, or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients are masked to treatment allocation. The study coprimary endpoints are rPFS and OS.
Abiraterone efficacy was first assessed in the overall population and then in the population who received ADT with docetaxel as standard of care (population of interest).
Between 27 November 2013 and 20 December 2018, a total of 1173 patients were enrolled, but one patient subsequently withdrew consent for analysis of data. Patients were assigned to receive standard of care (296 patients), standard of care plus radiotherapy (293 patients), standard of care plus abiraterone (292 patients), or standard of care plus radiotherapy plus abiraterone (291 patients).
Median follow-up was 3.5 years for rPFS and 4.4 years for OS. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy.
In the overall population, patients assigned to receive abiraterone (583 patients) had longer rPFS (hazard ratio [HR] 0.54, 99.9% confidence interval [CI] 0.41–0.71; p < 0.0001) and OS (HR 0.82, 95.1% CI 0.69–0.98; p = 0.030) than 589 patients who did not receive abiraterone. Among patients who received abiraterone, median rPFS was 4.46 years and median OS was 5.72 years, compared with median rPFS of 2.22 years and median OS of 4.72 years among those not receiving abiraterone.
In the ADT with docetaxel population (355 patients in both with abiraterone and without abiraterone groups), the HRs were consistent for both, rPFS (HR 0.50, 99.9% CI 0.34–0.71; p < 0.0001) and OS (HR 0.75, 95.1% CI 0.59–0.95; p = 0.017). Among patients who received abiraterone plus ADT with docetaxel, median rPFS was 4.46 years and median OS not reached compared with median rPFS of 2.03 years and median OS of 4.43 years among those not receiving abiraterone.
In the ADT with docetaxel population, grade 3 or worse adverse events occurred in 217 of 347 patients (63%) who received abiraterone and 181 of 350 patients (52%) who did not. Hypertension had the largest difference in occurrence, 76 patients (22%) and 45 patients (13%), respectively. Addition of abiraterone to ADT plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with ADT plus docetaxel alone.
The authors commented that the triplet therapy could become a standard of care for patients with de novo metastatic castration-sensitive prostate cancer.
The study was funded by Janssen-Cilag, Ipsen, Sanofi, and the French government.
Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet; Published online 8 April 2022. DOI: https://doi.org/10.1016/S0140-6736(22)00367-1