A PEACE of the action.

Top Line: A few weeks back, we read about the ARASENS trial where the addition of darolutamide to ADT and docetaxel for metastatic castration sensitive prostate cancer (mCSPC) reduced the risk of death by 32.5% and increased overall survival at 4 years from 50.4→ 62.7%.

The Study: Currently, doublet therapy with ADT and an androgen axis inhibitor or docetaxel is standard treatment for mCSPC, but the PEACE-1 trial follows close on the heels of ARASENS asking a very similar question about first-line triplet therapy. Men (n=1173) with de novo, synchronous mCSPC were randomized to 1 of 4 different arms: standard ADT (+/- docetaxel), standard treatment plus abiraterone, standard treatment plus radiation, or standard treatment plus abiraterone and RT. In 2015, the trial was amended so that docetaxel was added as an option in the standard arm and then made mandatory in 2017 after trials showing that the addition of docetaxel, and separately abiraterone to ADT improved survival. Ultimately, there were close to 300 men in each arm, and 60-61% received ADT plus docetaxel as their standard treatment. Here we have an initial analysis looking at the addition of abiraterone. There was no apparent interaction between radiation and abiraterone, so the arms with and without abiraterone (regardless of RT) were compared. Abiraterone significantly prolonged median radiographic progression free survival from 2.22→ 4.46 years with a 46% reduction in the risk of progression. It also prolonged median overall survival from 4.72→ 5.72 years with an 18% reduction in the risk of death. In addition, CRPC-free survival was prolonged from 1.5→ 3.8 years.  These benefits held true when analyzed according to patients who received docetaxel as part of their standard treatment. While rPFS was improved regardless of metastatic disease burden, the overall survival benefit was mainly seen among those with a high burden of disease. Wait, what about radiation? Those results will be analyzed according to the burden of metastatic disease and reported separately at a later time.

TBL: Two randomized trials now show that first-line triplet therapy with ADT, docetaxel, and a next-generation androgen axis inhibitor improves survival compared to standard doublet therapy. The survival benefit is most pronounced in those with high burden disease, but even those with low burden disease derive a significant reduction in the risk of progression. | Fizazi, Lancet Oncol 2022