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European Urology Dec 2022Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide,... (Meta-Analysis)
Meta-Analysis Review
Androgen Receptor Signaling Inhibitors in Addition to Docetaxel with Androgen Deprivation Therapy for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis.
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.
Topics: Humans; Male; Docetaxel; Androgen Antagonists; Androgens; Receptors, Androgen; Antineoplastic Combined Chemotherapy Protocols; Prostatic Neoplasms
PubMed: 35995644
DOI: 10.1016/j.eururo.2022.08.002 -
European Urology Focus Jan 2023Two recent randomized controlled trials (RCTs) reported overall survival benefit of triplet therapy (androgen receptor axis-targeted therapy agent [ARAT], docetaxel, and... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Two recent randomized controlled trials (RCTs) reported overall survival benefit of triplet therapy (androgen receptor axis-targeted therapy agent [ARAT], docetaxel, and androgen deprivation therapy [ADT]) over that of doublet therapy (docetaxel and ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ranking of therapy options and comparisons between triplet therapy and doublet ARAT and ADT therapy are scarce.
OBJECTIVE
To rank therapy options (triplet vs doublet [docetaxel and ADT] vs doublet [ARAT and ADT]) and address them within formal network meta-analyses (NMAs); subsequently, NMAs were refitted following stratification according to (1) low- and high-volume tumor burden and (2) doublet versus triplet therapy.
EVIDENCE ACQUISITION
A systematic literature review (PubMed, MEDLINE, Embase, Web of Science, Scopus, and Cochrane database) of RCT trials that investigated the overall survival efficacy of systemic treatment in the setting of mHSPC was conducted. The study search and inclusion criteria were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
EVIDENCE SYNTHESIS
Ten RCTs (n = 9702) were identified. The NMA focusing on the overall cohort of mHSPC demonstrated that triplet therapies (darolutamide, docetaxel, and ADT, and abiraterone, docetaxel, and ADT) were ranked first and second (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44-0.66; HR: 0.60; 95% CI: 0.46-0.78), followed by doublet therapy (ARAT and ADT) and lastly docetaxel and ADT. Owing to missing data within one RCT, the NMA for low- and high-volume mHSPC focused on nine trials. In high-volume disease, triplet therapy (abiraterone, docetaxel, and ADT) was ranked first (HR: 0.52, 95% CI: 0.38-0.71).
CONCLUSIONS
Triplet therapy, consisting of an ARAT, docetaxel, and ADT, ranked first in systematic treatment in mHSPC. Moreover, triplet therapy might result in more pronounced overall survival benefit than doublet ARAT and ADT therapy in high-volume mHSPC.
PATIENT SUMMARY
We compared different systemic therapy options for metastatic hormone-sensitive prostate cancer and concluded that triplet therapy, consisting of androgen receptor axis-targeted therapy agent, docetaxel, and androgen deprivation therapy, seems to be most beneficial for overall survival. Back to top.
Topics: Male; Humans; Docetaxel; Network Meta-Analysis; Androgens; Receptors, Androgen; Androgen Antagonists; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Prostatic Neoplasms
PubMed: 36058809
DOI: 10.1016/j.euf.2022.08.007 -
BJU International Apr 2022To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available treatments for the management of metastatic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available treatments for the management of metastatic hormone-sensitive prostate cancer (mHSPC), as there has been a paradigm shift with the use of next-generation androgen receptor inhibitors (ARIs) and docetaxel.
METHODS
Multiple databases were searched for articles published before May 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis extension statement for network meta-analysis. Studies comparing overall/progression-free survival (OS/PFS) and/or adverse events (AEs) in patients with mHSPC were eligible.
RESULTS
Nine studies (N = 9960) were selected, and formal network meta-analyses were conducted. Abiraterone (hazard ratio [HR] 0.83, 95% credible interval [CrI] 0.76-0.90), docetaxel (HR 0.90, 95% CrI 0.82-0.98), and enzalutamide (HR 0.85, 95% CrI 0.73-0.99) were associated with significantly better OS than androgen-deprivation therapy (ADT), and abiraterone emerged as the best option. Abiraterone (HR 0.71, 95% CrI 0.67-0.76), apalutamide (HR 0.73, 95% CrI 0.65-0.81), docetaxel (HR 0.84, 95% CrI 0.78-0.90), and enzalutamide (HR 0.67, 95% CrI 0.63-0.71) were associated with significantly better PFS than ADT, and enzalutamide emerged as the best option. Abiraterone (HR 0.85, 95% CrI 0.78-0.93), apalutamide (HR 0.87, 95% CrI 0.77-0.98), and enzalutamide (HR 0.80, 95% CrI 0.73-0.88) were significantly more effective than docetaxel. Regarding AEs, apalutamide was the likely best option among the three ARIs. In patients with low-volume mHSPC, enzalutamide was the best option in terms of OS and PFS.
CONCLUSIONS
All three ARIs are effective therapies for mHSPC; apalutamide was the best tolerated. All three seemed more effective than docetaxel. These findings may facilitate individualised treatment strategies and inform future comparative trials.
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Docetaxel; Hormones; Humans; Male; Network Meta-Analysis; Prostatic Neoplasms
PubMed: 34171173
DOI: 10.1111/bju.15507 -
European Urology Oncology Dec 2022Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear.
OBJECTIVE
To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments.
EVIDENCE ACQUISITION
We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate.
EVIDENCE SYNTHESIS
Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial.
CONCLUSIONS
Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies.
PATIENT SUMMARY
We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.
Topics: Male; Humans; Docetaxel; Network Meta-Analysis; Androgens; Prostatic Neoplasms
PubMed: 35599144
DOI: 10.1016/j.euo.2022.04.007 -
European Urology Oncology Jun 2023Androgen receptor signaling inhibitor (ARSi) agents are emerging as standard treatments for prostate cancer across the disease spectrum, but much remains unknown... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Androgen receptor signaling inhibitor (ARSi) agents are emerging as standard treatments for prostate cancer across the disease spectrum, but much remains unknown regarding how their side-effect profiles compare.
OBJECTIVE
To systematically evaluate the literature regarding adverse events (AEs) between the ARSi drugs abiraterone, apalutamide, darolutamide, and enzalutamide in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic CRPC (nmCRPC), and metastatic castration-sensitive prostate cancer (mCSPC).
EVIDENCE ACQUISITION
PubMed, Web of Science, and Embase were queried for double-blind, randomized controlled trials (RCTs) of ARSi therapy up to September 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Two teams reviewed titles and abstracts, and 14 RCTs were included for analysis.
EVIDENCE SYNTHESIS
Forest plots were used to summarize risk ratios for the most common AEs. According to surface under the cumulative ranking curve (SUCRA) values, enzalutamide was ranked as the most toxic treatment regarding hypertension outcomes (SUCRA 0%, most likely to be the bottom-ranked treatment) in both mCRPC and nmCRPC (SUCRA 0%). Enzalutamide was also ranked as the most toxic regarding headache across all prostate cancer entities (SUCRA 0%, for mCRPC, 1% for nmCRPC, and 3% for mCSPC).
CONCLUSIONS
Our findings suggest that the ARSi side-effect profiles do not significantly differ, except that enzalutamide was ranked the most toxic regarding hypertension in mCRPC and nmCRPC, and the most toxic regarding headache across all prostate cancer settings. These results highlight the importance of close blood-pressure monitoring for enzalutamide, and future research should explore possible connections between cardiovascular and neurological risk with ARSi therapy. In addition, these comparisons rely on the validity of cross-trial comparisons.
PATIENT SUMMARY
We reviewed the side-effect profiles of second-generation antiandrogen drugs for the treatment of prostate cancer. Side effects were similar, apart from higher risk of high blood pressure and headache risk with enzalutamide.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Network Meta-Analysis; Androgen Receptor Antagonists; Headache; Randomized Controlled Trials as Topic
PubMed: 36682938
DOI: 10.1016/j.euo.2023.01.001 -
JAMA Oncology Jul 2023The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.
OBJECTIVE
To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.
DATA SOURCES
PubMed, EMBASE, and Scopus (inception to September 12, 2022).
STUDY SELECTION
Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, fatigue, weakness), or falls were evaluated.
DATA EXTRACTION AND SYNTHESIS
Study screening, data abstraction, and bias assessment were completed independently by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Enhancing the Quality and Transparency of Health Research reporting guidelines. Tabular counts for all-grade toxic effects were determined to test the hypothesis formulated before data collection.
MAIN OUTCOMES AND MEASURES
Risk ratios (RRs) and SEs were calculated for cognitive toxic effects, asthenic toxic effects, and falls. Because fatigue was the asthenic toxic effect extracted from all studies, data on fatigue are specified in the results. Meta-analysis and meta-regression were used to generate summary statistics.
RESULTS
The systematic review included 12 studies comprising 13 524 participants. Included studies had a low risk of bias. An increased risk of cognitive toxic effects (RR, 2.10; 95% CI, 1.30-3.38; P = .002) and fatigue (RR, 1.34; 95% CI, 1.16-1.54; P < .001) was noted among individuals treated with second-generation AAs vs those in the control arms. The findings were consistent in studies that included traditional hormone therapy in both treatment arms for cognitive toxic effects (RR, 1.77; 95% CI, 1.12-2.79; P = .01) and fatigue (RR, 1.32; 95% CI, 1.10-1.58; P = .003). Meta-regression supported that, across studies, increased age was associated with a greater risk of fatigue with second-generation AAs (coefficient, 0.75; 95% CI, 0.04-0.12; P < .001). In addition, the use of second-generation AAs was associated with an increased risk of falls (RR, 1.87; 95% CI, 1.27-2.75; P = .001).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that second-generation AAs carry an increased risk of cognitive and functional toxic effects, including when added to traditional forms of hormone therapy.
Topics: Humans; Male; Androgen Antagonists; Androgen Receptor Antagonists; Androgens; Cognition; Fatigue; Prospective Studies; Prostatic Neoplasms; Quality of Life; Retrospective Studies
PubMed: 37227736
DOI: 10.1001/jamaoncol.2023.0998 -
Panminerva Medica Mar 2023Anabolic-androgenic steroids (AASs) are a complex cluster of synthetic derivatives of testosterone. AAS abuse is considered a major public health issue since it has...
INTRODUCTION
Anabolic-androgenic steroids (AASs) are a complex cluster of synthetic derivatives of testosterone. AAS abuse is considered a major public health issue since it has increased among young/adolescent males. The use of steroids has a prevalence rate of 14% in young athletes and 30-75% in professional athletes or bodybuilders. AASs simulate the testosterone mechanism, binding the intracellular androgen receptor, and dysregulating the normal hypothalamic-pituitary-gonadal axis in the same way as exogenous testosterone. Abuse can produce several side effects on organs, such as the genital system. The physio-pathological mechanisms that cause AAS abuse-related, genital system disorders in humans are still not completely known.
EVIDENCE ACQUISITION
This study focuses on the effect of AASs on the male reproductive organs in humans and animals.
EVIDENCE SYNTHESIS
A systematic review was performed using SCOPUS, PubMed, Google Scholar, and Web of Sciences database up to 31 December 2021 using the keywords: "anabolic-androgenic steroids," "erectile dysfunction," "spermatogenesis" and "infertility;" (anabolic agents) "erectile dysfunction," "spermatogenesis" and "infertility." The review of the literature identified 66 articles published until 2021. Sixty-two articles were included. The use of AASs induces testicular atrophy and azoospermia known as "anabolic steroid-induced hypogonadism." Anabolic steroid induced infertility is characterized by oligo or azoospermia and abnormalities in sperm motility and morphology. Although sperm quality recovers in most cases within 4 months of stopping anabolic steroid abuse, the negative consequences on spermatogenesis can take up to 3 years to disappear. Human studies reported a positive correlation between AAS abuse in athletes and an increase in morphologically abnormal spermatozoa. Animal studies showed the destruction of Leydig cells and testicular atrophy in animals treated with cycles of AASs.
CONCLUSIONS
The present review of the literature highlights how little is known about the action of AASs on the male genital system. However, although their use is prohibited in many countries, the black market for these substances is still very frequent. The scientific landscape still has a lot to invest in the research of AAS on the male genital system to make young people even more aware of the negative aspects of these substances, contributing to the reduction of these products in an inappropriate way.
Topics: Male; Humans; Adolescent; Anabolic Androgenic Steroids; Erectile Dysfunction; Azoospermia; Semen; Sperm Motility; Testosterone Congeners; Testosterone; Anabolic Agents; Steroids
PubMed: 35146992
DOI: 10.23736/S0031-0808.22.04677-8 -
Andrology Sep 2023Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men with obesity-related functional androgen deficiency.
OBJECTIVE
To determine whether and to what extent selective estrogen receptor modulators are an effective and safe therapy in men with obesity-related functional androgen deficiency.
MATERIALS AND METHODS
A thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases was performed to identify studies comparing testosterone levels before and after treatment. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias.
RESULTS
Seven studies met the inclusion criteria providing information on 292 men with obesity-related functional androgen deficiency treated with clomiphene citrate (12.5-50 mg daily) or enclomiphene citrate (12.5-25 mg daily) for 1.5-4 months. The pooled estimates indicated a significant increase in testosterone levels both with clomiphene (mean difference: 11.56 nmol/L; 95% coefficient interval: 9.68, 13.43; I = 69%, p = 0.01) and enclomiphene citrate (mean difference: 7.50 nmol/L; 95% coefficient interval: 6.52, 8.48; I = 4%, p = 0.37). After the exclusion of one study on severely obese men, who exhibited the highest response rate to clomiphene citrate, the heterogeneity disappeared (mean difference: 10.27 nmol/L; 95% coefficient interval: 9.39, 11.16; I = 0%, p = 0.66). No publication bias was revealed by Egger's test and trim-and-fill analysis. No treatment-related unexpected findings regarding safety profile were registered.
DISCUSSION AND CONCLUSION
Treatment with clomiphene citrate and enclomiphene citrate may be an effective and safe alternative to testosterone replacement therapy in men with obesity-related functional androgen deficiency. Further long-term studies are warranted to define clinical reflections of the selective estrogen receptor modulators-induced increase in testosterone levels and to better clarify the safety profile.
Topics: Humans; Male; Androgens; Clomiphene; Enclomiphene; Eunuchism; Hypogonadism; Obesity; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Testosterone
PubMed: 36604313
DOI: 10.1111/andr.13373 -
Seminars in Oncology Oct 2022Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic... (Meta-Analysis)
Meta-Analysis Review
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Radiation Oncologists; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36192243
DOI: 10.1053/j.seminoncol.2022.09.005 -
Frontiers in Endocrinology 2023econd-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
econd-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer patients, but some researchers have shown that using SGARIs increases side effects, which complicates clinicians' choice of. Therefore, we performed this network meta-analysis to assess the efficacy and toxicity of several SGARIs in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC).
METHODS
We searched PubMed, EMBASE and Cochrane Library databases from January 2000 to December 2022 to identify randomized controlled studies associated with SGARIs. We use Stata 16.0 and R 4.4.2 for data analysis, hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
This meta-analysis included 7 studies with a total of 9488 patients. In mHSPC, enzalutamide and darolutamide had a positive effect on overall survival (OS) (HR, 0.70; 95% CI, 0.59-0.82), but we did not find a difference in their efficacy to improve OS (HR, 1.19; 95% CI, 0.75-1.89). Also in nmCRPC, enzalutamide, apalutamide and darolutamide were beneficial for metastasis-free survival (MFS) (HR, 0.32; 95% CI, 0.25-0.41). Compared to darolutamide, enzalutamide (HR, 0.71; 95% CI, 0.54-0.93) and apalutamide (HR, 0.68; 95% CI, 0.51-0.91) prolonged MFS, but there was no difference in efficacy between enzalutamide and apalutamide (HR, 0.97; 95% CI, 0.73-1.28). Finally in mCRPC, there was no significant difference in indirect effects on OS between pre- and post-chemotherapy enzalutamide (HR, 0.89; 95% CI, 0.70-1.13). However, using enzalutamide before chemotherapy to improve radiographic progression-free survival (rPFS) was a better option (HR, 2.11; 95% CI, 1.62-2.73).
CONCLUSION
The SGARIs used in each trial were beneficial for the primary endpoint in the study. Firstly there was no significant difference in the effect of enzalutamide and darolutamide in improving OS in patients with mHSPC. Secondly improving MFS in patients with nmCRPC was best achieved with enzalutamide and apalutamide. In addition both pre- and post-chemotherapy use of enzalutamide was beneficial for OS in mCRPC patients, but for improving rPFS pre-chemotherapy use of enzalutamide should be preferred.The INPLASY registration number of this systematic review is INPLASY202310084.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Network Meta-Analysis; Phenylthiohydantoin; Androgen Receptor Antagonists
PubMed: 36967752
DOI: 10.3389/fendo.2023.1134719