Top Line: Recently, two randomized trials, ARASENS and PEACE-1, showed that triplet therapy for metastatic, castration sensitive prostate cancer improves overall survival.
The Study: By “triplet therapy” we mean the combination of ADT, an androgen receptor pathway inhibitor (darolutamide in ARASENS and abiraterone in PEACE-1), and docetaxel. Compared to the doublet of ADT and docetaxel, triplet therapy improved overall survival in both trials. In practice, though, many patients don’t start with triplet therapy, and they typically progress stepwise through each line of therapy. It often goes something like this: ADT → add androgen receptor pathway inhibitor → drop androgen receptor pathway inhibitor and add docetaxel. PRESIDE was a randomized, phase 3 trial designed to determine if continuing the androgen receptor pathway inhibitor after progression and during next-line therapy with docetaxel (e.g. triplet therapy) would improve outcomes for men with mCRPC. 688 patients were enrolled in the first phase of the trial and they started enzalutamide after progressing to mCRPC on ADT. Of these, 57.4% had either radiographic or PSA progression. 70% of those were eligible to be randomized to receive docetaxel with or without continuation of enzalutamide. The continuation of enzalutamide modestly, but significantly improved median PFS from 8.3 to 9.5 months. The PSA response was more significant (45% v 25%) than the radiographic response (41% v 39%). There was no difference in the time to skeletal events. While overall toxicity was similar between arms, there were more serious toxicity events in the enzalutamide arm.
TBL: Continuing enzalutamide after progression when switching to docetaxel for mCRPC may modestly improve PFS at the expense of an increased risk of toxicity.
- Merseburger, Lancet Oncol 2022