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Clinical Genitourinary Cancer Dec 2022The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive... (Review)
Review
The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.
Topics: Male; Humans; Docetaxel; Abiraterone Acetate; Cost-Benefit Analysis; Treatment Outcome; Prostatic Neoplasms; Hormones
PubMed: 35610112
DOI: 10.1016/j.clgc.2022.04.014 -
Acta Oncologica (Stockholm, Sweden) Nov 2022Osimertinib is a recently approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osimertinib is a recently approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790M resistance mutations. The aim of the present meta-analysis was to investigate the efficacy and safety of osimertinib for patients with EGFR-mutated non-small-cell lung cancer (NSCLC).
MATERIALS AND METHODS
Databases were searched for randomized controlled studies that reported the efficacy and safety of osimertinib versus other treatments (chemotherapy, other EGFR-TKIs, etc.) in treating EGFR-mutated NSCLC. The measured effects included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), central nervous system progression-free survival (CNS-PFS), and overall survival (OS). Additional outcome was the incidence of adverse event. Relative risk (RR) for incidence and hazard ratio (HR) for survival outcomes were pooled.
RESULTS
Seven studies containing 3335 participants were finally included. Osimertinib tended to improve ORR and DCR (RRs >1) as compared with other treatments. Osimertinib was also a significant protective factor for PFS, CNS-PFS, and OS (HRs <1 and < .05). Osimertinib showed similar advantages in improving tumor response and patient survival when used as first-line, second-line, and third-line/adjuvant therapy, respectively, as compared with other treatments (RRs >1 for ORR and DCR; HRs <1 for PFS, CNS-PFS, and OS). Osimertinib also had better therapeutic effects as compared with chemotherapy, other EGFR TKIs, docetaxel + bevacizumab, and placebo, respectively. The five most common adverse events with pooled incidence > 20% were diarrhea, rash, nail effects, dry skin, and stomatitis, yet the pooled incidence of serious adverse events was less than 2%.
CONCLUSIONS
This meta-analysis suggests that osimertinib has a positive effect in disease control and survival for patients with EGFR-mutated NSCLC with acceptable toxicities.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 36240432
DOI: 10.1080/0284186X.2022.2132116 -
Critical Reviews in Oncology/hematology Apr 2024To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs)... (Meta-Analysis)
Meta-Analysis Review
Second-line treatment options in metastatic castration-resistant prostate cancer after progression on first-line androgen-receptor targeting therapies: A systematic review and Bayesian network analysis.
OBJECTIVE
To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs) for biomarker-unselected metastatic castration-resistant prostate cancer (mCRPC) patients.
METHODS
Studies published in English up to May 2023 were identified in PubMed, Web of Science and ASCO-GU 2023. Studies accessing the efficacy and safety of second-line systematic therapies after first-line ARTs for biomarker-unselected mCRPC patients were eligible for current systematic review and network meta-analysis (NMA).
RESULTS
Thirty-two studies with 5388 patients and 10 unique treatment modalities met our inclusion criteria. Current evidence suggested that docetaxel (DOC) combined with the same ART as first-line (ART1) (ART1 + DOC) were associated with significantly improved PSA response, PSA progression-free survival (PFS) and clinical or radiographic PFS (rPFS) compared with other reported second-line systematic therapies, including DOC. An increase in toxicity was observed with ART1 + DOC. Our NMA indicated that DOC monotherapy was only inferior to ART1 + DOC in improvement disease outcomes. The incidence of toxicity between patients received second-line DOC and an alternative ART (ART2) was similar.
CONCLUSION
The available evidence reviewed in our work suggested a clinical benefit of DOC nomotherapy and DOC plus ART1 as the second-line systematic therapy for biomarker-unselected mCRPC patients progressed on a first-line ART. More studies and RCTs are needed to evaluate the optimal second-line treatments for mCRPC patients with one prior first-line ART.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgens; Prostate-Specific Antigen; Treatment Outcome; Bayes Theorem; Docetaxel; Biomarkers; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38316286
DOI: 10.1016/j.critrevonc.2024.104286 -
Frontiers in Pharmacology 2023To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic...
To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Qualified publications were searched in the PubMed, Embase, and Cochrane CENTRAL databases. Overall survival (OS) and radiographic progression-free survival (rPFS) were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve, respectively. Adverse events (AEs) were also compared. Eighteen publications from 12 trials were analyzed in the NMA. In the overall population, triplet therapy was ranked first for OS (hazard ratio [HR]: 0.57, 95% credible interval [CrI]: 0.48-0.67) and rPFS (HR: 0.33, 95% CrI:0.26-0.41) compared with androgen deprivation therapy (ADT) with or without standard non-steroidal antiandrogen. In high-volume mHSPC, triplet therapy was also ranked first in OS (HR, 0.57; 95% CrI:0.44-0.75) and rPFS(HR, 0.29; 95% CrI: 0.23-0.37). Specifically, abiraterone triplet therapy was ranked first in OS (HR, 0.52; 95% CrI:0.38-0.72) and rPFS (HR, 0.28; 95% CrI:0.21-0.38) among all therapies. ADT plus rezvilutamide was ranked first among doublet therapies (OS: HR, 0.58; 95% CrI:0.44-0.77; rPFS: HR, 0.44; 95% CrI:0.33-0.58). In low-volume mHSPC, doublet and triplet therapies were ranked first in OS (HR:0.68, 95% CrI:0.58-0.80) and rPFS (HR:0.37, 95% CrI:0.25-0.55), respectively. ADT plus apalutamide was ranked first in OS among all therapies (HR:0.53, 95% CrI:0.35-0.79), whereas enzalutamide triplet therapy was ranked first in rPFS (HR:0.27, 95% CrI:0.15-0.51). ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapies (OR:1.00, 95% CrI:0.31-3.15), and a lower risk of specific AEs among doublet therapies, particularly regarding seizure (OR, 0.29; 95% CrI:0.01-8.18) and fatigue (OR, 0.96; 95% CrI:0.63-1.46). Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs. Triplet therapy was the best treatment option for the overall population. In high-volume mHSPC, triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients. Patients with low-volume mHSPC were most likely to benefit from ADT plus androgen receptor-targeted agents. Triplet therapy was associated with a higher risk of AEs than the other therapies. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375347, identifier PROSPERO:CRD42022375347.
PubMed: 37153773
DOI: 10.3389/fphar.2023.1148021 -
Cancers Mar 2022The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2)... (Review)
Review
The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the "Quality Assessment of Prognostic Accuracy Studies" tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [Ga]PSMA-11 (16 articles/1123 patients) or [C]/[F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [Ga]PSMA-11, three with [C]Choline, one with [F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [F]Choline PET/CT ( = 121 patients) and three with [Ga]PSMA-11 PET ( = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [F]Choline and [Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario.
PubMed: 35406542
DOI: 10.3390/cancers14071770 -
European Urology Jul 2022Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC).
OBJECTIVE
To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC.
EVIDENCE ACQUISITION
We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes.
EVIDENCE SYNTHESIS
We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile.
CONCLUSIONS
Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT.
PATIENT SUMMARY
Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.
Topics: Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Humans; Male; Prospective Studies; Prostatic Neoplasms
PubMed: 35465985
DOI: 10.1016/j.eururo.2022.03.031 -
Indian Journal of Urology : IJU :... 2022Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This...
INTRODUCTION
Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This study was designed using the network meta-analysis (NMA) framework to provide a comparison of the different available options for the treatment of men with mCSPC.
METHODS
A systematic search was performed and the prospective randomized controlled trials reporting the overall survival (OS) or failure-free survival (FFS) were selected for review. A total of 14 studies were included in the NMA.
RESULTS
The addition of abiraterone, apalutamide, docetaxel, and docetaxel with zoledronic acid to the androgen deprivation therapy (ADT) demonstrated a significant improvement in the OS. In indirect comparison, abiraterone had a higher impact on the OS as compared to docetaxel (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.0-1.46) and docetaxel with zoledronic acid (HR: 1.31, 95% CI: 1.05-1.63) but not apalutamide. Furthermore, apalutamide was not different than docetaxel or docetaxel with zoledronic acid. There was a significant improvement in the FFS with the combination of abiraterone, apalutamide, docetaxel (HR: 0.61, 95% CI: 0.46-0.81), docetaxel with zoledronic acid (HR: 0.62, 95% CI: 0.43-0.9), and enzalutamide (HR: 0.39, 95% CI: 0.25-0.61) as compared to the ADT alone. Similar to the indirect comparison of OS, abiraterone outperformed docetaxel (HR: 1.66, 95% CI: 1.12-2.47), docetaxel with zoledronic acid (HR: 1.69, 95% CI: 1.06-2.68), and enzalutamide (HR: 1.06, 95% CI: 0.63-1.80), but not apalutamide in terms of impact on the FFS.
CONCLUSION
Overall, abiraterone demonstrated better OS and FFS outcomes as compared to all the other combination strategies in this NMA.
PubMed: 35983120
DOI: 10.4103/iju.iju_402_21 -
Frontiers in Pharmacology 2022To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for...
To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC). We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated. Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57-0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59-0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39-0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30-0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68-12.63; OR: 1.07, 95% CrI: 0.03-36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15-2.11). Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.
PubMed: 36278154
DOI: 10.3389/fphar.2022.955925 -
Journal of Gastrointestinal Oncology Apr 2023Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This...
Paclitaxel combined with platinum (PTX) versus fluorouracil combined with cisplatin (PF) in the treatment of unresectable esophageal cancer: a systematic review and meta-analysis of the efficacy and toxicity of two different regimens.
BACKGROUND
Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This study aimed to systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the concurrent chemoradiotherapy (CCRT) of unresectable esophageal cancer.
METHODS
The PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar and Embase databases were searched by combining subject words and free words through December 31, 2021. The inclusion criteria were pathologically confirmed esophageal cancer studies using CCRT, where the chemotherapy regimen only compared PTX and PF. Quality evaluation and data extraction of studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used to perform the meta-analysis. The begger analysis and egger analysis were used to assess publication bias, and the robustness of the pooled results further assessed by the Trim and Fill analysis.
RESULTS
After screening, 13 randomized controlled trials (RCTs) were included. A total of 962 cases were enrolled, including 480 (49.9%) in the PTX group and 482 (50.1%) in the PF group. The gastrointestinal reaction to the PF regimen was the most serious [relative risk (RR) =0.54, 95% confidence interval (CI): 0.36-0.80, P=0.003]. The complete remission (CR) rate, objective response rate (ORR), and disease control rate (DCR) of the PTX group were higher than those of the PF group (RR =1.35, 95% CI: 1.03-1.76, P=0.030; RR =1.12, 95% CI: 1.03-1.22, P=0.006; RR =1.05, 95% CI: 1.01-1.09, P=0.022). In terms of the overall survival (OS) rate, the 2-year survival rates of the PTX group were higher than those of the PF group (P=0.005). There was no significant difference in the 1-, 3-, and 5-year survival rates between the two regimens (P=0.064, 0.144, and 0.341, respectively). There may be publication bias for ORR and DCR, and the results are reversed after applying the Trim and Fill method, so the combined results are not robust.
CONCLUSIONS
PTX may be the preferred regimen for CCRT of esophageal squamous cell carcinoma, with better short-term therapeutic effect and 2-year OS rate and lower gastrointestinal toxicity.
PubMed: 37201087
DOI: 10.21037/jgo-23-33 -
Drug Development Research Aug 2023This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the... (Review)
Review
This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the development of new TNBC chemotherapy sensitivity biomarkers and therapeutic targets. The PubMed, Embase, Web of Knowledge, Cochrane Library, and four Chinese databases were searched up to January 27, 2023, and studies related to TNBC chemoresistance were included. The basic characteristics of the studies and the mechanisms of circRNAs in regulating TNBC chemoresistance were analyzed. A total of 28 studies published between 2018 and 2023 were included, and the chemotherapeutics included adriamycin, paclitaxel, docetaxel, 5-fluorouracil, lapatinib, and so forth. A total of 30 circRNAs were identified, 86.67% (n = 26) of these circRNAs were reported to act as microRNA (miRNA) sponges to regulate chemotherapy sensitivity, while only two circRNAs (circRNA-MTO1 and circRNA-CREIT) interacted with proteins. A total of 14, 12, and 2 circRNAs were reported to be associated with chemoresistance to adriamycin, taxanes, and 5-fluorouracil, respectively. Six circRNAs were found to act as miRNA sponges that promote chemotherapy resistance by regulating the PI3K/Akt signalling pathway. CircRNAs participate in the regulation of TNBC chemoresistance and can be used as biomarkers and therapeutic targets for improving chemotherapy sensitivity. However, further studies are needed to confirm the role of circRNAs in TNBC chemoresistance.
Topics: Humans; RNA, Circular; Triple Negative Breast Neoplasms; Drug Resistance, Neoplasm; Phosphatidylinositol 3-Kinases; MicroRNAs; Biomarkers; Doxorubicin; Fluorouracil; Gene Expression Regulation, Neoplastic
PubMed: 37114737
DOI: 10.1002/ddr.22069