Table 2. Overall Survival With Doublet Therapy (API or Docetaxel) Compared With ADT by Volume of Disease.
| Population | Total participantsa | Hazard ratio (95% CI)b | P value of interactionc | Interpretation |
|---|---|---|---|---|
| Overall patient populationb | ||||
| API doublet | 6808 | 0.69 (0.62-0.76) | .06 | API doublet therapy derived greater OS benefit than docetaxel doublet therapy compared with ADT alone. There was statistically significant effect modification by choice of doublet therapy in the overall population. |
| Docetaxel doublet | 2261 | 0.79 (0.71-0.89) | ||
| High volume | ||||
| API doublet | 3443 | 0.66 (0.60-0.73) | .26 | In patients with high-volume disease, there was consistent OS benefit with API and docetaxel doublets compared with ADT alone. There was no effect modification by choice of doublet therapy in high-volume disease. |
| Docetaxel doublet | 1164 | 0.73 (0.62-0.86) | ||
| Low volume | ||||
| API doublet | 1983 | 0.58 (0.49-0.68) | <.01 | In patients with low-volume disease, API doublet therapy derived significantly greater OS benefit than docetaxel doublet therapy compared with ADT alone. There was statistically significant effect modification by choice of doublet therapy in low-volume disease. |
| Docetaxel doublet | 841 | 0.91 (0.73-1.13) |
Abbreviations: ADT, androgen deprivation therapy; API, androgen pathway inhibitors (including abiraterone acetate, apalutamide, and enzalutamide); ENZAMET, Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer; OS, overall survival; STAMPEDE, Systemic Therapy in Advancing or Metastatic Prostate Cancer, Evaluation of Drug Efficacy.
“Total participants” represents the total number of participants who were included in each comparison, which includes the number of participants in the treatment group and the number in the control for a comparison. The STAMPEDE trial4,6 followed an adaptive multigroup and multistage randomized design in which active experimental treatments groups were assessed with a shared control group. Hence, there may be overlap of patients included for abiraterone or docetaxel comparisons from STAMPEDE.
All effect estimates (hazard ratios) are for doublet regimens compared with standard ADT. These comparisons include only trials that assessed the efficacy of addition of API or docetaxel to standard ADT relative to ADT only. We assumed the relative efficacy of ADT to be similar to ADT plus nonsteroidal antiandrogen, which was the comparator in the ENZAMET trial3 for the purpose of pooling studies for direct comparisons. These comparisons do not include evidence from trials assessing triplet therapy relative to docetaxel and ADT (ARASENS9 and PEACE-18).
Statistical significance was established at a prespecified 2-sided α threshold of .10.