Researchers, led by Irbaz Riaz from the Dana Farber Cancer Institute, performed a living review of phase 2 and 3 randomized controlled trials in order to rank first-line treatment options for patients with metastatic castration-sensitive prostate cancer (mCSPC). Their findings were presented at the ESMO Congress 2022.
Riaz reported that triplet therapy with darolutamide (DARO) or abiraterone acetate and prednisone (AAP) plus docetaxel (D) and androgen deprivation therapy (ADT) significantly improved overall survival (OS) compared with doublet D and ADT, but not compared with novel hormonal therapy (NHT) doublets.
The review included a total of 10 randomized controlled trials with 11,043 patients and 9 unique treatments. Primary measures of interest included OS, progression-free survival (PFS), and grade 3 or higher adverse events (AEs). The researchers used a fixed-effect frequentist network meta-analysis to rank treatment options.
In the overall population, DARO triplet was ranked 1 (hazard ratio [HR], 0.68; 95% CI, 0.58-0.81), and AAP triplet was ranked 2 (HR, 0.75; 95% CI, 0.59-0.95). D and ADT alone was ranked 6. In patients with high-volume disease, AAP triplet was ranked 1 and significantly improved disease compared with D and ADT (rank 5; HR, 0.72; 95% CI, 0.55-0.95), but not compared with AAP and ADT (rank 2), enzalutamide (E) and ADT (rank 3), and apalutamide (APA) and ADT (rank 4).
Conversely, in patients with low-volume disease, AAP triplet was ranked 4 and did not significantly improve OS compared with APA and ADT (rank 1), AAP and ADT (rank2), E and ADT (rank 3), and D and ADT (rank 5). Outcomes for PFS were consistent with OS findings. Notably, both DARO and AAP triplets were ranked the lowest (rank 8 and 7, respectively) for incidence of grade 3 or higher AEs.
Overall, Riaz cautioned that volume of disease must be accounted for when weighing potential benefits of triplet therapy. Ultimately, the researchers suggested that “triplets may be favored in high volume whereas NHT doublets may be a preferred option in low volume of disease.”
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