KEY TAKEAWAYS
- The ARCHES (NCT02677896), a phase 3 trial, was used in the network meta-analysis.
- An NMA of RCTs was conducted to compare the effectiveness of ADT plus ARAT versus the combination of ADT, ARAT, and docetaxel in mHSPC.
- In its early stages, the triplet regimen exhibited the highest efficacy and optimal therapeutic approach for mHSPC.
- The study did not find a statistically significant OS advantage compared to the combination of ADT and ARAT
- Further research may be needed to determine the best treatment approach for mHSPC.
Clinical studies have demonstrated that the incorporation of docetaxel or androgen receptor axis-targeted therapy (ARAT) into androgen deprivation therapy (ADT), or the addition of ARAT to ADT and docetaxel, leads to enhanced overall survival (OS) in individuals with metastatic hormone-sensitive prostate cancer (mHSPC). These studies were randomized controlled trials (RCTs). The independent overall survival benefit of docetaxel in triplet therapy is currently uncertain. This study aimed to conduct a network meta-analysis (NMA) of randomized controlled trials (RCTs) in metastatic hormone-sensitive prostate cancer (mHSPC). The objective was to compare the effectiveness of androgen deprivation therapy (ADT) plus androgen receptor axis-targeted agents (ARAT) versus the combination of ADT, ARAT, and docetaxel. In March 2022, a search was conducted on bibliographic databases and conference proceedings to identify randomized controlled trials (RCTs) that assessed the efficacy of docetaxel, ARAT, or a combination of both in conjunction with androgen deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). The main outcome measure was overall survival.
A routine application of random-effect network meta-analysis (NMA) and Bayesian analyses was conducted to compare the efficacy of androgen deprivation therapy (ADT) in combination with abiraterone acetate and prednisone (ARAT) versus triplet therapy. Eleven randomized controlled trials (n = 11,546) met the inclusion criteria. In comparison to ADT plus ARAT, the triplet exhibited an insignificant benefit in overall survival (OS) with a hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.68-1.16. Conversely, ADT plus docetaxel (HR 1.16 [0.94-1.43]) and ADT alone (HR 1.46 [1.30-1.64]) were associated with an elevated risk of mortality. According to the P-score ordering, the triplet exhibited the highest efficacy as a treatment strategy (P score = 0.936), while ADT plus ARAT (P score = 0.704) was the second most effective option. According to the statistical analysis, the triplet regimen exhibited a higher probability of being the optimal therapeutic approach, with a 77% chance, in contrast to a 23% chance for ADT plus ARAT. The therapeutic regimen consisting of ADT, ARAT, and docetaxel was ranked as the most effective; however, it did not provide a statistically significant overall survival advantage compared to the combination of ADT and ARAT. This Network Meta-Analysis (NMA) presents the most superior comparative evidence for managing metastatic hormone-sensitive prostate cancer (mHSPC) in its early stages.
Source: https://pubmed.ncbi.nlm.nih.gov/35811293/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02677896
Roy S, Sayyid R, Saad F, Sun Y, Lajkosz K, Ong M, Klaassen Z, Malone S, Spratt DE, Wallis CJD, Morgan SC. Addition of Docetaxel to Androgen Receptor Axis-targeted Therapy and Androgen Deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis. Eur Urol Oncol. 2022 Oct;5(5):494-502. doi: 10.1016/j.euo.2022.06.003. Epub 2022 Jul 8. PMID: 35811293.
