Androgen Receptor Signaling Inhibitors in Addition to Docetaxel with Androgen Deprivation Therapy for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis
Language English Country Switzerland Media print-electronic
Document type Meta-Analysis, Systematic Review, Journal Article, Review, Research Support, Non-U.S. Gov't
PubMed
35995644
DOI
10.1016/j.eururo.2022.08.002
PII: S0302-2838(22)02551-9
Knihovny.cz E-resources
- Keywords
- Androgen receptor signaling inhibitor, Docetaxel, Metastatic hormone-sensitive prostate cancer,
- MeSH
- Receptors, Androgen MeSH
- Androgens therapeutic use MeSH
- Androgen Antagonists * adverse effects MeSH
- Docetaxel therapeutic use MeSH
- Humans MeSH
- Prostatic Neoplasms * pathology MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Systematic Review MeSH
- Names of Substances
- Receptors, Androgen MeSH
- Androgens MeSH
- Androgen Antagonists * MeSH
- Docetaxel MeSH
- enzalutamide MeSH Browser
CONTEXT: Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide, darolutamide (DAR), and enzalutamide (ENZ), to docetaxel (DOC) and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: To analyze the oncologic benefit of triplet combination therapies using ARSI + DOC + ADT, and comparing them with available treatment regimens in patients with mHSPC. EVIDENCE ACQUISITION: Three databases and meetings abstracts were queried in April 2022 for RCTs analyzing patients treated with first-line combination systemic therapy for mHSPC. The primary interests of measure were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were conducted to assess the differential outcomes in patients with low- and high-volume disease as well as de novo and metachronous metastasis. EVIDENCE SYNTHESIS: Overall, 11 RCTs were included for meta-analyses and network meta-analyses (NMAs). We found that the triplet combinations outperformed DOC + ADT in terms of OS (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.84) and PFS (pooled HR: 0.49, 95% CI: 0.42-0.58). There was no statistically significant difference between patients with low- and high-volume disease in terms of an OS benefit from adding an ARSI to DOC +ADT (both HR: 0.79; p = 1). Based on NMAs, triplet therapy also outperformed ARSI + ADT in terms of OS (DAR + DOC + ADT: pooled HR: 0.74, 95% CI: 0.55-0.99) and PFS (ABI + DOC + ADT: HR: 0.68, 95% CI: 0.51-0.91, and ENZ + DOC + ADT: HR: 0.70, 95% CI: 0.53-0.93). An analysis of treatment ranking among de novo mHSPC patients showed that triplet therapy had the highest likelihood of improved OS in patients with high-volume disease; however, doublet therapy using ARSI + ADT had the highest likelihood of improved OS in patients with low-volume disease. CONCLUSIONS: We found that the triplet combination therapy improves survival endpoints in mHSPC patients compared with currently available doublet treatment regimens. Our findings need to be confirmed in further head-to-head trials with longer follow-up and among various patient populations. PATIENT SUMMARY: Our study suggests that triplet therapy with androgen receptor signaling inhibitor, docetaxel, androgen deprivation therapy prolongs survival in patients with metastatic hormone-sensitive prostate cancer compared with the current standard doublet therapy.
Department of Urology The Jikei University School of Medicine Tokyo Japan
Unit of Urology Division of Oncology IRCCS San Raffaele San Raffaele Hospital Milan Italy
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