1417P - Mixed treatment comparisons evaluating contemporary therapies in metastatic castration sensitive prostate cancer (mCSPC): A living systematic review

Background

Results from recent trials (PEACE-1, and ARASENS), the disease heterogeneity in mCSPC and lack of direct comparisons between triplets and novel hormonal therapy (NHT) doublets prompted us to assess the comparative effectiveness of contemporary treatments accounting for volume of disease.

Methods

This living review was conducted using the living interactive evidence (LIvE) synthesis framework. Phase II/III randomized controlled trials (RCTs) assessing first-line treatment options in mCSPC were included. Outcomes of interest included overall survival (OS), progression free survival (PFS), and grade 3 or higher adverse events (AEs). Fixed-effect frequentist network meta-analysis (NMA) was conducted to compute mixed treatment comparisons. P-scores were used to assess the relative treatment rankings.

Results

Of 28791 studies identified till date (25^th April 2022), a total of 10 RCTs with 11043 patients and 9 unique treatment arms are included in this living review. In overall population, darolutamide triplet (DARO+D+ADT; rank 1; HR 0.68; 95% CI: 0.57-0.81), abiraterone acetate triplet (AAP+D+ADT; rank 2; HR 0.75; 95% CI: 0.59-0.95) significantly improved OS compared to docetaxel (D)+ADT (rank 6) but not compared to NHT doublets. In patients with high volume of disease, AAP+D+ADT (rank 1) significantly improved OS compared to D+ADT (rank 5; HR: 0.72; 95% CI: 0.55-0.95) but not compared to AAP+ADT (rank 2), enzalutamide (E)+ADT (rank 3), and apalutamide (APA)+ADT (rank 4). In low volume of disease, AAP+D+ADT (rank 4) did not significantly improve OS compared to APA+ADT (rank 1), AAP+ADT (rank 2), E+ADT (rank 3), and D+ADT (rank 5). The results were consistent excluding patients who received docetaxel in ENZAMET, ARCHES, and TITAN trials. The results were consistent for PFS outcome. DARO+D+ADT and AAP+D+ADT were ranked as the least safe options (rank 8, and 7, respectively) in terms of grade 3 or higher AEs.

Conclusions

The potential benefit with triplet therapy must be interpreted with caution accounting for volume of disease. Triplets may be favored in high volume whereas NHT doublets may be a preferred option in low volume of disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Irbaz Bin Riaz.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.