Late-breaking data from 2 randomized phase 3 trials that followed the STAMPEDE protocol were presented at the ESMO Congress 2022. These trials compared abiraterone acetate and prednisolone (AAP) to AAP with enzalutamide in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initiating androgen deprivation therapy (ADT).
First author and presenter, Gerhardt Attard, reported that the recorded data suggests there is no need to combine enzalutamide with AAP in patients with mHSPC. The studies also showed that clinically important improvements in overall survival (OS) from the addition of AAP to ADT were sustained at year 7.
STAMPEDE is a multi-arm, multi-stage platform protocol conducted across 117 centers in the UK and Switzerland. The 2 trials presented at EMSO Congress 2022 included 1003 patients randomized to ADT with or without AAP and 916 patients randomized to ADT with or without AAP plus enzalutamide. The trialists used meta-analysis methods to evaluate differences in OS, as well as failure-free, metastatic progression-free, progression-free, and prostate-cancer-specific survival.
In the AAP plus enzalutamide trial, OS was improved relative to ADT alone in patients with mHSPC (hazard ratio [HR], 0.65; 95% CI, 0.55-0.77; P=1.4×10-6). The benefit was similar to that observed in the AAP without enzalutamide trial (HR, 0.62; 95% CI, 0.53-0.73; P=1.6×10-9). The researchers established there were no differences in treatment effect (interaction HR, 0.1.05; 95% CI, 0.83-1.32; P=.71) or between-trial heterogeneity (I2 P=.70). Results were similar for the secondary survival end points.
Regarding toxicity, grade 3-5 toxicities in the first 5 years of the ADT and AAP trial were reported in 38.5% of patients on ADT alone (95% CI, 34.2-42.8) and in 54.4% of patients on ADT and AAP (95% CI, 50.0-58.8). Comparatively, in the AAP plus enzalutamide trial, 45.2% of patients on ADT alone (95% CI, 40.6-49.8) and 67.9% of patients on ADT and AAP plus enzalutamide (95% CI, 63.5-72.2) experienced equivalent toxicities. The most commonly reported events in both trials were liver derangement and hypertension.
Overall, Attard and colleagues’ results supported the addition of AAP to patients with mHSPC initiating ADT to improve survival. Results further indicated that enzalutamide did not provide any additional benefit when added alongside AAP.