Comparison of Systemic Treatments for Metastatic Castration-Resistant Prostate Cancer After Docetaxel Failure: A Systematic Review and Network Meta-analysis

Abstract

Background: Lacking head-to-head trial, the optimal treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure is unclear. This study is to compare the efficacy and safety of systemic treatments in patients who progressed after docetaxel to aid clinical decision-making.Methods: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched from inception to June 15th, 2021. The outcomes of interest include overall survival (OS), biochemical progression-free survival (bPFS), and serious adverse events (SAEs). The Cochrane risk of bias tools were used to assess study quality. Indirect comparisons of competing treatments were performed via Bayesian network meta-analysis.Results: Five trials with 3,862 patients comparing four treatments (abiraterone, enzalutamide, cabazitaxel, and radium-223) were identified. All the four treatments were associated with improved OS and bPFS relative to best supportive care. Among them, enzalutamide (hazard ratio [HR] = 0.58, 95% credible interval [Crl]: 0.49–0.69) had the highest probability of ranking first in terms of OS, followed by cabazitaxel (HR = 0.70, 95% Crl: 0.59–0.83), radium-223 (HR = 0.71, 95% Crl: 0.56–0.90) and abiraterone (HR = 0.73, 95% Crl: 0.63–0.84). Similarly, enzalutamide (HR = 0.25, 95% Crl: 0.20–0.31) showed the greatest improvement of bPFS, followed by abiraterone (HR = 0.60, 95% Crl: 0.51–0.71) and cabazitaxel (HR = 0.75, 95% Crl: 0.63–0.89). In terms of safety, treatments ranked from the safest to the least safe were radium-223 (OR = 0.58, 95% Crl: 0.20–1.68), enzalutamide (OR = 0.80, 95% Crl: 0.28–2.29), abiraterone (OR = 0.94, 95% Crl: 0.39–2.27) and cabazitaxel (OR = 2.50, 95% Crl: 0.84–7.44).Conclusion: For patients with mCRPC who progressed after docetaxel, enzalutamide may offer the most significant survival benefits and satisfying safety. Cabazitaxel is effective in post-docetaxel settings but associated with a high risk of SAEs. Although network meta-analysis provides indirect comparisons and ranking probabilities, the results should be treated with caution as it cannot replace randomized direct comparison.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020223040, identifier CRD42020223040.

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review

“…Nonetheless, most studies agreed that ENZ patients demonstrate increased biochemical or radiographic response. Although significance is difficult to achieve given variable patient populations and small cohort sizes, it appears that ENZ is demonstrably superior in disease control [ 4 , 49 ].…”

“…Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer in men, accounting for over 20% of new cancer cases [ 1 , 2 , 3 , 4 ]. Abiraterone acetate (AA), an androgen biosynthesis inhibitor, and enzalutamide (ENZ), an androgen receptor signaling inhibitor, are novel hormonal therapies (NHTs) that are mainstay additions to androgen deprivation therapy in PCa, particularly in metastatic disease [ 5 , 6 , 7 , 8 , 9 , 10 ].…”

Integrating transcriptomics and network analysis-based multiplexed drug repurposing to screen drug candidates for M2 macrophage-associated castration-resistant prostate cancer bone metastases

“…Tumor pathogenesis usually involves pathological features characterized by redundancy and versatility, limiting the clinical efficacy of single-target drugs. However, drug combination therapy often results in complex pharmacodynamic or pharmacokinetic interactions, or both, due to individual differences and other factors, which makes it difficult to describe the effectiveness and side effects of combined drugs, and may bring additional health issues ( 75 ). The evaluation of drug absorption, distribution, metabolism, excretion and toxicity characteristics is of great significance for predicting drug interactions.…”

Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis

“…For metastatic hormone-sensitive prostate cancer (mHSPC), androgen-deprivation therapy (ADT) has been regarded as the standard of care (SOC) and the only systematic treatment option for a long time (3). However, patients receiving ADT will inevitably gradually resist the treatment and enter the stage of castration resistance (mCRPC), which will significantly worsen the prognosis (4)(5)(6). Delaying the progression of metastatic prostate cancer to mCRPC has always been an important topic in the field of prostate cancer treatment.…”

“…In addition, ADT combined with radiotherapy (RT) (18) is considered to provide survival benefits for mHSPC patients with low volume disease (LVD). The emergence of these novel combination therapies is significantly changing the previous standard of care for mHSPC using ADT alone, but the advantages and disadvantages of these combination therapies are controversial due to the lack of head-to-head comparisons (4,7,8,(19)(20)(21)(22)(23)(24).…”