First results from the phase 3 PEACE-1 trial show that adding abiraterone to androgen deprivation therapy (ADT) plus docetaxel significantly improves progression-free survival in patients who present de novo metastatic castration-sensitive prostate cancer (mCSPC) without meaningful added short-term toxicity.
Historically, ADT was the standard of care for men with mCSPC. Since 2015, combining ADT with either docetaxel, novel hormonal therapies (abiraterone, enzalutamide), or radiotherapy to the primary tumour was shown to improve overall survival and thus became the new standard of care1-4. However, it is unknown whether combining these new treatments on top of ADT further increments outcomes.
The primary goal of the PEACE-1 trial (NCT01957436) is to evaluate the efficacy and safety of the addition of abiraterone, radiotherapy, or abiraterone plus radiotherapy to standard of care. A total of 1,173 men with de novo mCSPC were randomised to standard of care, standard of care plus abiraterone, standard of care plus radiotherapy, or standard of care plus abiraterone plus radiotherapy. No interaction was detected between the effect of abiraterone and that of radiotherapy (P=0.64), allowing to pool abiraterone arms for comparisons: 589 patients were enrolled in the standard of care (± radiotherapy) arm and 583 patients were enrolled in the standard of care (± radiotherapy) plus abiraterone arm.
The trial has 2 co-primary endpoints of radiographic progression-free survival and overall survival. Dr Karim Fizazi (Institut Gustav Roussy, France) presented the first results of PEACE-15. After a median follow-up of 3.5 years, median radiographic progression-free survival was 4.5 years in the standard of care plus abiraterone arm versus 2.2 years in the standard of care arm. Median castration-resistant-free survival was 3.8 years and 1.5 years, respectively. Relative improvement of progression-free survival was comparable in patients treated with or without docetaxel.
No meaningful additional toxicity was observed in patients treated with standard of care plus abiraterone. “Adding abiraterone to ADT or to ADT plus docetaxel significantly improves progression-free survival in men with de novo metastatic prostate cancer, with about 2.5 years of absolute benefit in medians, and no meaningful additional short-term toxicity,” Dr Fizazi concluded.
1. Sweeney CJ, et al. N Engl J Med 2015; 373:737-746.
2. Fizazi K, et al. N Engl J Med 2017; 377:352-360.
3. Davis ID, et al. N Engl J Med 2019; 381:121-131.
4. Parker CC, et al. Lancet 2018; 392: 2353-2366.
5. Fizazi K, et al. A phase 3 trial with a 2x2 factorial design of abiraterone acetate plus prednisone and/or local radiotherapy in men with de novo metastatic castration-sensitive prostate cancer (mCSPC): First results of PEACE-1. ASCO 2021 Virtual Meeting, abstract 5000.