Findings from the PEACE-1 trial published in the Lancet showed that adding abiraterone acetate (Zytiga) and prednisone to androgen-deprivation therapy (ADT) and docetaxel improved overall survival (OS) and radiographic progression-free survival rPFS in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC).1
In the phase 3 trial (NCT01957436), researchers randomized 1173 men with de novo mCSPC (57% high-volume and 43% low-volume) to receive standard of care (SOC) – which was ADT continuously with or without 75 mg/m2/3w for 6 cycles docetaxel (n = 296), SOC plus 1000 mg per day of abiraterone plus 5 mg twice daily of prednisone (n = 292), SOC plus 74 grades of radiotherapy to the primary tumor (RXT) (n = 293), or SOC plus abiraterone plus RXT (n = 292).
Trial candidates included men with de novo mCSPC who may have received up to 3 months of ADT before randomization for the study. The stratification factors were ECOG performance status (PS) (0 vs 1-2), site of metastasis (lymph node vs bone vs visceral), type of castration (orchidectomy vs LHRH-agonist vs LHRH-antagonist), and the use of docetaxel.
Patient characteristics were well-balanced between arms, as expected in such a large trial. Specifically regarding the 710 men who received ADT plus docetaxel as their SOC, about two-thirds of them had high metastatic burden – with 63% in the SOC +/- RXT + abiraterone arm (n = 355) and 65% in the SOC +/- RXT arm (n = 355).
Other notable characteristics included a median age of 66 in both arms, an ECOG PS score of 0 in most patients (70% and 69%, respectively), and 1-2 in the remaining (30% and 31%, respectively). Median time from diagnosis was 2.2 (IQR, 1.6-3.0) in the SOC +/- RXT + abiraterone arm and 2.2 (IQR, 1.4-2.9) in the SOC +/- RXT arm. Most patients in both arms had metastasis in the bone without visceral – 81% in the SOC +/- RXT + abiraterone arm and 79% in the SOC +/- RXT arm – while 8% of both arms had it in the lymph nodes, and 12% and 13%, respectively, had visceral metastasis.
The co-primary endpoints were rPFS and OS, and “PEACE-1 used a factorial design…answering 2 questions: the role of abiraterone and that of radiotherapy on top of SOC. The number of events for the abiraterone analysis has been reached, while a longer follow-up is needed to assess the role of radiotherapy,” according to the authors.
The co-primary endpoint of rPFS was reached in the ADT plus docetaxel (+/- RXT) population (HR, 0.50; 95% CI, 0.40-0.62; P <.0001). It reduced the risk of radiographic progression or death by a median of 4.5 years with abiraterone, compared with 2 years without. Men with low- (HR, 0.58; 95% CI, 0.39-0.87; P <.006) and high-volume (HR, 0.47; 95% CI, 0.36-0.60; P <.0001) disease alike saw benefit with abiraterone.
Median follow-up in the overall population was 4.4 years, 5.7 in the ADT alone +/- RXT arm, and 3.8 in the ADT + docetaxel +/- RXT arm. OS was improved with abiraterone in the overall population (HR, 0.83; 95% CI, 0.69-0.99; P = .034) as well as in the ADT + docetaxel population (HR, 0.75; 95% CI, 0.59-0.96; P = .021).
For patients with high metastatic burden, adding abiraterone to ADT plus docetaxel reduced the risk of death by 28%. However, for men with low-volume disease, the medians have not yet been reached in either arm.
In terms of adverse events – which were generally balanced between arms – there were grade 3-5 events in more than 5% of patients in the ADT plus docetaxel population. These included neutropenic fever (5% vs 5%), neutropenia (10% vs 9%), liver toxicity (6% vs 1%), and hypertension (21% vs 13%) in the abiraterone and control arms, respectively.
When previously presenting the PEACE-1 findings at the 2021 ESMO Annual Congress, lead study author Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy and professor of Oncology at the University of Paris-Saclay in Villejuif, France, said, “We believe data are practice-changing. At the least, men with de novo high volume metastatic prostate cancer should be offered ADT plus docetaxel plus abiraterone based on evidence that this treatment combination will provide 2.5 years additional time without radiographic progression or death, and 1.5 additional years of survival.”
1. 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 April 8, 2022. doi: https://doi.org/10.1016/S0140-6736(22)00367-1