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Metastatic renal cell cancer treatments: an indirect comparison meta-analysis.

ABSTRACT: Treatment for metastatic renal cell cancer (mRCC) has advanced dramatically with understanding of the pathogenesis of the disease. New treatment options may provide improved progression-free survival (PFS). We aimed to determine the relative effectiveness of new therapies in this field.We conducted comprehensive searches of 11 electronic databases from inception to April 2008. We included randomized trials (RCTs) that evaluated bevacizumab, sorafenib, and sunitinib. Two reviewers independently extracted data, in duplicate. Our primary outcome was investigator-assessed PFS. We performed random-effects meta-analysis with a mixed treatment comparison analysis.We included 3 bevacizumab (2 of bevacizumab plus interferon-a [IFN-a]), 2 sorafenib, 1 sunitinib, and 1 temsirolimus trials (total n = 3,957). All interventions offer advantages for PFS. Using indirect comparisons with interferon-alpha as the common comparator, we found that sunitinib was superior to both sorafenib (HR 0.58, 95% CI, 0.38-0.86, P = < 0.001) and bevacizumab + IFN-a (HR 0.75, 95% CI, 0.60-0.93, P = 0.001). Sorafenib was not statistically different from bevacizumab +IFN-a in this same indirect comparison analysis (HR 0.77, 95% CI, 0.52-1.13, P = 0.23). Using placebo as the similar comparator, we were unable to display a significant difference between sorafenib and bevacizumab alone (HR 0.81, 95% CI, 0.58-1.12, P = 0.23). Temsirolimus provided significant PFS in patients with poor prognosis (HR 0.69, 95% CI, 0.57-0.85).New interventions for mRCC offer a favourable PFS for mRCC compared to interferon-alpha and placebo.

SUBMITTER: Mills EJ

PROVIDER: S-EPMC2637892 | biostudies-other | 2009 Jan

REPOSITORIES: biostudies-other

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Metastatic renal cell cancer treatments: an indirect comparison meta-analysis.

Mills Edward J EJ Rachlis Beth B O'Regan Chris C Thabane Lehana L Perri Dan D

BMC cancer 20090127

<h4>Background</h4>Treatment for metastatic renal cell cancer (mRCC) has advanced dramatically with understanding of the pathogenesis of the disease. New treatment options may provide improved progression-free survival (PFS). We aimed to determine the relative effectiveness of new therapies in this field.<h4>Methods</h4>We conducted comprehensive searches of 11 electronic databases from inception to April 2008. We included randomized trials (RCTs) that evaluated bevacizumab, sorafenib, and sunit ...[more]

PMID: 19173737

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Project description:BackgroundFor nonmetastatic castration-resistant prostate cancer (nmCRPC), 3 drugs under patent protection-apalutamide, enzalutamide, and darolutamide-were approved based on randomized, placebo-controlled trials; 1 drug with generic availability, abiraterone acetate, showed efficacy in a single-arm trial and is commonly prescribed. Lacking head-to-head trials, the optimal treatment for nmCRPC is unknown, despite widely varied treatment costs. We compared the efficacy and safety of nmCRPC treatments.MethodsWe searched bibliographic databases, regulatory documents, and trial registries for nmCRPC trials. We included published results and, when available, original data. We performed matching-adjusted indirect comparison and network meta-analysis and compared treatments regarding metastasis-free survival, overall survival, and serious adverse events.ResultsWe analyzed 5 trials with 4360 participants. Compared with placebo, abiraterone acetate engendered the lowest hazard of metastasis and death (hazard ratio [HR] = 0.22, 95% credible interval [CrI] = 0.12-0.41), followed by apalutamide (HR = 0.28, 95% CrI = 0.23-0.34), enzalutamide (HR = 0.30, 95% CrI = 0.25-0.36), and darolutamide (HR = 0.41, 95% CrI = 0.34-0.49); darolutamide led to the lowest hazard of death (HR = 0.69, 95% CrI = 0.53-0.90), followed by enzalutamide (HR = 0.73, 95% CrI = 0.61-0.87) and apalutamide (HR = 0.75, 95% CrI = 0.59-0.95); darolutamide resulted in the lowest odds of serious adverse events (odds ratio [OR] = 1.32, 95% CrI = 1.02-1.70), followed by enzalutamide (OR =1.43, 95% CrI = 1.08-1.89), apalutamide (OR = 1.58, 95% CrI = 1.23-2.03), and abiraterone acetate (OR = 1.94, 95% CrI = 1.17-3.22).ConclusionsFor nmCRPC, darolutamide offered optimal efficacy and safety among approved drugs, and abiraterone acetate may offer comparable metastasis-free survival benefit with cost savings from generic availability. Future research is needed to more fully examine the benefit of abiraterone acetate.

Project description:ImportanceMultiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs.ObjectiveTo compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC.Data sourcesBibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019.Study selection, data extraction, and synthesisEligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.Main outcomes and measuresOverall survival, radiographic progression-free survival, and serious adverse events (SAEs).ResultsSeven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [CI], 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89); treatments associated with improved radiographic progression-free survival when added to ADT included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI, 13.37-45.15), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses.Conclusions and relevanceIn this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.

Project description: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.

Project description:BackgroundThe objective of this study is to evaluate the efficacy and safety of different third-line treatment regimens for metastatic colorectal cancer (mCRC) through a comprehensive analysis and network meta-analysis (NMA). Additionally, the study aims to provide guidance on selecting appropriate third-line systemic treatment regimens for patients with mCRC.MethodsWe conducted a search of the PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases from January 1, 2005, to May 20, 2023, to include phase II/III randomized clinical trials (RCTs) of third-line treatments for mCRC. The primary outcome assessed in the NMA was median overall survival (mOS), and other outcomes included median progression-free survival (mPFS), disease control rate (DCR), and grade 3 or higher adverse events (≥3AEs).ResultsUltimately, nine phase II/III RCTs involving five treatment regimens were included in this study. Trifluridine/tipiracil (TAS-102) plus bevacizumab (hazard ratio [HR] 0.41, 95% credible interval [CrI] 0.32-0.52) was found to be the most effective treatment for mOS compared to best supportive care (BSC). TAS-102 plus bevacizumab also significantly improved mPFS compared to BSC (HR 0.20, 95% CrI 0.16-0.25). In terms of adverse events (AEs), TAS-102 (RR 0.52, 95% CrI 0.35-0.74) had a lower incidence of ≥3AEs compared to fruquintinib, but fruquintinib (RR 1.79, 95% CrI 1.10-3.11) showed better improvement in DCR than TAS-102. Subgroup analysis using the Bayesian surface under the cumulative ranking curve (SUCRA) ranked the regimens based on the OS benefit. The results indicated that TAS-102 plus bevacizumab ranked first across age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), and time from initial diagnosis of metastatic disease to randomization.ConclusionTAS-102, fruquintinib, TAS-102 plus bevacizumab, the regorafenib standard dose regimen (regorafenib), and the regorafenib dose-escalation regimen (regorafenib 80+) all demonstrated improved OS and PFS compared to BSC in mCRC patients. However, TAS-102 plus bevacizumab may be the optimal choice for third-line treatment in mCRC patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php, CRD42023434929.

Dataset Information

Metastatic renal cell cancer treatments: an indirect comparison meta-analysis.

Publications

Metastatic renal cell cancer treatments: an indirect comparison meta-analysis.

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