Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile: an updated systematic review and meta-analysis

2021 ◽  
Author(s):  
Keiichiro MORI ◽  
Fahad QUHAL ◽  
Satoshi KATAYAMA ◽  
Hadi MOSTAFAEI ◽  
Ekaterina LAUKHTINA ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Safety Profile ◽  
Meta Analysis ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

2021 ◽  
Author(s):  
Mike Wenzel ◽  
Luigi Nocera ◽  
Claudia Collà Ruvolo ◽  
Christoph Würnschimmel ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
High Risk ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pubmed Search ◽  
Grade 3 ◽  
Meta Analyses

Abstract Background The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives. Methods We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes. Results Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6–10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order. Conclusion The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.

A Systematic Review and Network Meta-analysis of Novel Androgen Receptor Inhibitors in Non-metastatic Castration-resistant Prostate Cancer

2020 ◽  
Vol 18 (5) ◽  
pp. 343-350 ◽  
Author(s):  
Amanda E. Hird ◽  
Diana E. Magee ◽  
Bimal Bhindi ◽  
Xiang Y. Ye ◽  
Thenappan Chandrasekar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Androgen Receptor ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Optimizing PSMA Radioligand Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Meta-Analysis

2020 ◽  
Vol 21 (23) ◽  
pp. 9054
Author(s):  
Finn Edler von Eyben ◽  
Glenn Bauman ◽  
Rie von Eyben ◽  
Kambiz Rahbar ◽  
Cigdem Soydal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Meta Analysis ◽  
Severe Adverse Effect ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Asymptomatic Patients

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of 177Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.

A Systematic Review and Meta-Analysis on the Predictive Value of Cell-Free DNA–Based Androgen Receptor Copy Number Gain in Patients With Castration-Resistant Prostate Cancer

2020 ◽  
pp. 714-729
Author(s):  
Sofie H. Tolmeijer ◽  
Emmy Boerrigter ◽  
Jack A. Schalken ◽  
Maartje J. Geerlings ◽  
Inge M. van Oort ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Androgen Receptor ◽  
Copy Number ◽  
Meta Analysis ◽  
Copy Number Gain ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Free Dna ◽  
Taxane Chemotherapy

PURPOSE It has been suggested that androgen receptor copy number gain ( AR gain) detected in cell-free DNA (cfDNA) can predict treatment response to androgen receptor signaling inhibitors (ARSIs) in patients with castration-resistant prostate cancer (CRPC). But it is unclear whether cfDNA-based AR gain is a true resistance mechanism to ARSIs or mainly a reflection of the tumor burden. In this systematic review, we aim to summarize current literature and comment on the potential of cfDNA-based AR gain as a predictive biomarker to guide therapy choices. METHODS A literature search was conducted in PubMed/Medline, Cochrane, Embase, and Web of Science databases. Sixteen articles published before November 2019 were selected for the meta-analysis, representing more than 1,000 patients. By using a random effects model, the progression-free survival (PFS) and overall survival (OS) were compared between patients with and without cfDNA-based AR gain who had been treated with ARSIs or with taxane chemotherapy. RESULTS Upon treatment with ARSIs, the PFS (hazard ratio [HR], 2.33; 95% CI, 2.00 to 2.72; P < .0001) and the OS (HR, 3.83; 95% CI, 3.11 to 4.70; P < .0001) were worse for patients with cfDNA-based AR gain, independent of the line and type of ARSIs. The OS and PFS in patients treated with first-line docetaxel or second-line or third-line cabazitaxel seemed to be unaffected by AR gain, despite a higher disease burden in patients with AR gain. AR gain was associated with reduced response with later lines of docetaxel. CONCLUSION In patients with CRPC, cfDNA-based AR gain is associated with a worse response to ARSIs. The effect on patients who are receiving taxane chemotherapy seems to be dependent on the type and line, although data are limited. Future prospective studies are essential to assess the true potential of cfDNA-based AR gain as a minimally invasive biomarker to guide therapy choice.

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