Metastatic castration-sensitive prostate cancer: When is it preferable to use triplet, doublet therapies?

In patients with metastatic castration-sensitive prostate cancer (mCSPC), triplet therapy may be ideal for fit patients with synchronous (de novo) high-volume disease while the androgen pathway inhibitor (API) doublet combinations may be preferred for those with metachronous (recurrent) low-volume disease, according to the results of a meta-analysis.

Researchers evaluated the comparative efficacy of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups. Multiple online databases were searched for phase III randomized clinical trials (RCTs) on first-line treatment options for mCSPC.

A total of 10 studies were identified for inclusion in the meta-analysis. These studies contributed to a total of 11,043 patients and nine unique treatment groups. The median ages of the included population ranged from 63 to 70 years. The overall risk of bias for overall survival was low across all trials, while some concerns were raised for the assessment of PFS and grade 3 or higher adverse events due to the open-label nature of several trials. 

Pooled data in the overall population showed that OS outcomes favoured the darolutamide triplet (darolutamide/docetaxel/androgen deprivation therapy [ADT]: hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.57–0.81) as well as the abiraterone triplet (abiraterone/docetaxel/ADT; HR, 0.75, 95 percent CI, 0.59–0.95) as compared with docetaxel doublet, but not when compared with API doublets.

Abiraterone/docetaxel/ADT significantly was associated with longer OS as compared with docetaxel/ADT (HR, 0.72, 95 percent CI, 0.55–0.95) but not when compared with abiraterone/ADT, enzalutamide/ADT, and apalutamide/ADT among patients with high-volume disease.

Meanwhile, API doublet therapies were ranked as the most efficacious treatment options and were not significantly different from triplet regimens for patients with low-volume disease.

The present data show how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.