Third treatment’s the charm.

Top Line: It’s been a minute since docetaxel or androgen receptor axis-targeted therapy (e.g., abiraterone, enzalutamide, etc.) became recommended additions to androgen deprivation therapy (ADT) for metastatic castrate sensitive prostate cancer.

The Study: But recently, two randomized trials (ARASENS and PEACE-1) showed that triplet therapy (ADT, ARAT, and docetaxel) improves overall survival for mCSPC. Both trials tested the addition of ARAT to ADT+docetaxel, and there wasn’t a separate comparison of the addition of docetaxel to ADT+ARAT. Enter this meta-analysis of 11 randomized trials that evaluated the addition of docetaxel, ARAT, or both to ADT for metastatic castrate sensitive prostate cancer. With ARAT + ADT as the comparator, ADT alone (HR 1.46) and even ADT + docetaxel (HR 1.16) had a significantly increased risk of death. Triplet therapy with docetaxel + ARAT + ADT, on the other hand, achieved the numerically longest survival time (HR 0.89), although the improvement in OS was not statistically significant. Sophisticated modeling determined triplet therapy has a 77% chance of being the most effective strategy to maximize survival times, followed by ARAT + ADT with a 23% likelihood. Proponents of triplet therapy point to early incorporation of cytotoxic chemo as an important strategy to eradicate castrate resistant clones borne from ARAT + ADT.

TBL: This meta-analysis supports the role of triplet therapy (ADT+ARAT+docetaxel) in men with mCSPC, however it questions the magnitude of benefit from the addition of docetaxel to ADT+ARAT in light of potential toxicity. | Roy, Eur Urol Oncol 2022