The addition of abiraterone acetate (Zytiga) and prednisone to androgen-deprivation therapy (ADT) and docetaxel improved radiographic progression-free survival (rPFS) in men with de novo metastatic castration-sensitive prostate cancer (mCSPC), according to initial results from the phase 3 PEACE-1 study (NCT01957436).1
The findings, which were presented at the 2021 ASCO Annual Meeting, showed that adding abiraterone/prednisone to standard docetaxel/ADT was associated with an approximately 2.5-year absolute benefit in median rPFS in this patient population.
The PEACE-1 study randomized men with de novo mCSPC in a 1:1:1:1 ratio to standard of care (SOC), SOC plus abiraterone acetate/prednisone, SOC plus radiotherapy (RT), or SOC plus abiraterone plus RT. Initially, SOC was ADT alone, but from October 2015 onward, the use of docetaxel was permitted. This was done at the investigator’s discretion until 2017, at which point, following the publication of the LATITUDE (NCT01715285) and STAMPEDE (NCT00268476) trials, docetaxel was mandatory.
Patient stratification was based on ECOG performance status, metastatic sites, type of castration, and docetaxel status.
The 2 coprimary end points were rPFS and overall survival. Key secondary end points included castration resistance–free survival, prostate cancer–specific survival, time to next skeletal-related event, PSA response rate, quality of life, and safety.
Between November 2013 and December 2018, 1173 men were enrolled. The median patient age was 67 years (interquartile range, 60-72). High-volume disease was present in 57% of patients, with 43% of patients having low-volume disease. Median follow-up was 3.5 years.
The investigators found no interaction between the effect of local RT and that of abiraterone on rPFS, which allowed the pooling of the 2 abiraterone arms for analysis. When divided into abiraterone and SOC arms, patient characteristics were similar between the arms.
The investigators reported a median rPFS of 4.5 years in the abiraterone arm in the overall population versus 2.2 years for SOC (P < .0001). Similarly, better rPFS was observed in the abiraterone arm versus the SOC arm in the ADT plus docetaxel population (4.5 vs 2.0 years; P <.0001). In addition, PFS including PSA progression as an event was also improved with abiraterone in both the overall population (3.8 vs 1.5 years; P <.0001) and the ADT plus docetaxel population (3.2 vs 1.4 years; P < .0001).
“Importantly, all tested subgroups pretty much seemed to benefit from the addition of abiraterone,” said lead study author Karim Fizazi, MD, PhD, head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France, and a professor of Oncology at the University of Paris-Sud.
In the docetaxel population, grade 3 to 5 toxicities that were higher in patients receiving abiraterone and docetaxel versus patients receiving docetaxel but not abiraterone included liver toxicities (6% vs 0%) and hypertension (12% vs 8%).
“It was very reassuring to see that abiraterone, even used concomitantly with docetaxel, did not increase the risk of febrile neutropenia…or other hematological toxicities related to docetaxel,” Fizazi said.
Grade 3 to 5 gastrointestinal toxicity and fatigue, which are typically associated with docetaxel, had a lower incidence in the group of patients receiving abiraterone (2% vs 4%), which Fizazi said may be due to the abiraterone cohort also receiving prednisone.
“In conclusion, adding abiraterone and prednisone to ADT plus docetaxel clearly improves radiographic PFS in men with de novo metastatic prostate cancer,” Fizazi said.
1. Fizazi K, Maldonado X, Foulon S, 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. J Clin Oncol 39, 2021 (suppl 15; abstr 5001). doi: 10.1200/JCO.2021.39.15_suppl.5000