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BMC Cancer Aug 2023Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast... (Meta-Analysis)
Meta-Analysis
Neoadjuvant immunotherapy and chemotherapy regimens for the treatment of high-risk, early-stage triple-negative breast cancer: a systematic review and network meta-analysis.
BACKGROUND
Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast cancer patients. Recently, neoadjuvant delivery of the programmed cell death protein-1 inhibitor pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was approved for patients with high-risk, early-stage TNBC, but this treatment regimen has not been evaluated in head-to-head trials with other neoadjuvant treatment regimens. Therefore, the objective of this study was to estimate the relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab versus other neoadjuvant treatments for early-stage TNBC through a systematic review and network meta-analysis (NMA).
METHODS
EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts, and clinical trial registries were searched for randomized controlled trials evaluating neoadjuvant treatments for early-stage TNBC. NMA was performed to estimate relative treatment effects among evaluated interventions.
RESULTS
Five trials met the inclusion criteria and were included in the NMA. The relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab was favorable to paclitaxel followed by anthracycline + cyclophosphamide in terms of pathologic complete response (pCR), event-free survival (EFS), and overall survival; paclitaxel + carboplatin followed by anthracycline + cyclophosphamide in terms of pCR and EFS; paclitaxel + bevacizumab followed by anthracycline + cyclophosphamide + bevacizumab in terms of pCR; and paclitaxel + carboplatin + veliparib followed by anthracycline + cyclophosphamide in terms of EFS.
CONCLUSIONS
Neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab confers benefits in response and survival outcomes versus alternative neoadjuvant treatments for early-stage TNBC.
Topics: Humans; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Network Meta-Analysis; Bevacizumab; Carboplatin; Neoplasm Recurrence, Local; Immunotherapy; Adjuvants, Immunologic; Anthracyclines; Cyclophosphamide; Paclitaxel
PubMed: 37612624
DOI: 10.1186/s12885-023-11293-4 -
Cureus Jul 2023The aim of this study is to assess and compare the effectiveness and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) and solvent-based PTX (sb-PTX) as... (Review)
Review
Nanoparticle Albumin‑Bound Paclitaxel and Solvent-Based Paclitaxel as Chemotherapy Options for Patients With Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.
The aim of this study is to assess and compare the effectiveness and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) and solvent-based PTX (sb-PTX) as treatment options for advanced gastric cancer. This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We carried out a comprehensive search of PubMed, Google Scholar, and EMBASE from inception to June 15, 2023. The search strategy included the following keywords: "Nanoparticle albumin-bound paclitaxel," "solvent-based paclitaxel," and "advanced gastric cancer," along with their synonyms and medical subject heading (MeSH) terms. In this meta-analysis, the primary outcome was the comparison of overall survival and progression-free survival between the two groups. For safety purposes, we compared the risk of hematological and non-hematological events between the two groups. Four studies were included in this meta-analysis enrolling 1052 patients (483 received nb-PTX and 569 received sb-PTX). In terms of efficacy, nab-PTX showed favorable trends in overall survival and progression-free survival, despite no statistically significant differences being reported. The subgroup meta-analysis showed that nab-PTX seemed to have a better effect on peritoneal metastasis compared to sb-PTX. Regarding safety, the number of patients with neutropenia and leucopenia was significantly higher in the nab-PTX group compared to the sb-PTX group. However, the difference was statistically insignificant. Future research should focus on conducting more robust studies to further validate these findings and establish a stronger evidence base for the use of nab-PTX in this patient population.
PubMed: 37575705
DOI: 10.7759/cureus.41711 -
Frontiers in Medicine 2023This meta-analysis was exerted in assessing the anticancer efficacy and safety of nab-paclitaxel (nab-P) when combined with platinum compound agents for therapy in...
PURPOSE
This meta-analysis was exerted in assessing the anticancer efficacy and safety of nab-paclitaxel (nab-P) when combined with platinum compound agents for therapy in patients with non-small cell lung cancer (NSCLC).
METHOD
We systematically searched the following seven electronic databases: PubMed, Cochrane Library, Web of Science, Embase, CNKI, Wan Fang, and China Science and Technology Journal Data. Randomized comparative clinical [randomized controlled clinical trial (RCT)] studies on nab-P plus platinum and carboplatin or cisplatin in combination with conventional chemotherapy agents or traditional paclitaxel were searched.
RESULTS
A total of 19 RCT studies involving 6,011 patients were analyzed. The primary outcome includes the overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The secondary outcome includes adverse events (AEs). Nab-P combined with platinum (carboplatin/cisplatin) had a better ORR [odds ratio (OR) = 1.66, 95% confidence interval (CI) (1.34, 2.05), < 0.001] and improved PFS [hazard ratio (HR) = 0.84, 95% CI: (0.74, 0.94), = 0.01] and OS [HR = 0.86, 95% CI: (0.78, 0.96), = 0.008] in NSCLC patients. ORR [OR = 2.18, 95% CI: (1.07, 4.43)], PFS [HR = 0.62, 95% CI: (0.40, 0.97)], and OS [HR = 0.63, 95% CI: (0.49, 0.81)] were significantly improved among patients aged >70 years, and ORR [OR = 1.80, 95% CI: (1.20, 2.70)] and PFS [HR = 0.74, 95% CI: (0.56, 0.97)] were significantly elevated with SCC rate ≥65% in NSCLC patients (all > 0.05). Among the adverse effects, the prevalence of neutropenia, neuralgia, and arthralgia/myalgia (≥ grade 3) compared to that of the control group. On the other hand, the prevalence of anemia and thrombocytopenia was higher in the nab-P plus platinum (carboplatin/cisplatin) compared to that of controls. It is worth noting that fatigue did not show statistical significance.
CONCLUSION
Nab-P in combination with carboplatin/cisplatin regimen improves efficacy and tolerability in patients with NSCLC.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022288499.
PubMed: 37554498
DOI: 10.3389/fmed.2023.1139248 -
Frontiers in Pharmacology 2023Malignant melanoma is a highly aggressive cancer that spreads and metastasizes quickly. In recent years, the antiangiogenic drug bevacizumab has been trialed to treat...
Efficacy and safety of bevacizumab in patients with malignant melanoma: a systematic review and PRISMA-compliant meta-analysis of randomized controlled trials and non-comparative clinical studies.
Malignant melanoma is a highly aggressive cancer that spreads and metastasizes quickly. In recent years, the antiangiogenic drug bevacizumab has been trialed to treat malignant melanoma. We conducted the first meta-analysis to examine the efficacy and safety of bevacizumab combined with other drugs in malignant melanoma. We searched for randomized controlled trials (RCTs) and non-comparative clinical studies of bevacizumab combined with chemotherapy, targeted medicine, and interferon to treat malignant melanoma in PubMed, Embase, the Cochrane Library, and Web of Science. Meta-analysis of RCT was performed using Review Manager (version 5.4), and non-comparative meta-analysis was performed using R (version 4.0.3). The primary outcome was the objective response rate. Depending on the heterogeneity of the included studies, the pooled outcomes and 95% CI were calculated using either random-effects or fixed-effect models. Subgroup outcomes were calculated with possible relevant variables. Sensitivity analyses were carried out by excluding each study from the highly heterogeneous pooled results in turn. Funnel plot and Begg's test were used to test the included studies' potential publication bias. The level of significance was set at < 0.05. This meta-analysis included 20 trials: five RCTs and 15 non-comparative clinical studies with a total of 23 bevacizumab intervention arms. In 14 treatment arms, bevacizumab was combined with chemotherapy drugs such as fotemustine, dacarbazine, carboplatin/paclitaxel, and temozolomide. In six treatment arms, bevacizumab was combined with targeted medicines such as imatinib, everolimus, sorafenib, erlotinib, and temsirolimus. There were also six treatment arms that used bevacizumab in combination with interferon. The pooled objective response rate was 15.8% (95% CI, 11.4%-20.2%). Bevacizumab plus carboplatin/paclitaxel significantly increased the overall survival compared to carboplatin/paclitaxel (HR = 0.64, 95% CI, 0.49-0.85, < 0.01). Fatigue, nausea, leukopenia, thrombocytopenia, and neutropenia were the most common adverse events. The pooled incidence of hypertension of all bevacizumab arms in malignant melanoma was 32.4% (95% CI, 24.5%-40.3%). This study showed that bevacizumab combined with chemotherapy might be effective and well-tolerated in patients with stage III or IV unresectable malignant melanoma. : [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=304625], identifier [CRD42022304625].
PubMed: 37521468
DOI: 10.3389/fphar.2023.1163805 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
Frontiers in Pharmacology 2023Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of...
Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of life and survivorship in affected patients. Genetic polymorphisms in the CYP3A family have been investigated but the findings have been inconsistent and contradictory. A systematic review identified 12 pharmacogenetic studies investigating genetic variation in and and TIPN. In our candidate gene study, 288 eligible participants (211 taxane participants receiving docetaxel or paclitaxel, and 77 control participants receiving oxaliplatin) were successfully genotyped for and . Genotyping data was transformed into a combined CYP3A metaboliser phenotype: Poor metabolisers, intermediate metabolisers and extensive metabolisers. Individual genotypes and combined CYP3A metaboliser phenotypes were assessed in relation to neurotoxicity, including by meta-analysis where possible. In the systematic review, no significant association was found between and TIPN in seven studies, with one study reporting a protective association. For , one study has reported an association with TIPN, while four other studies failed to show an association. Evaluation of our patient cohort showed that paclitaxel was found to be more neurotoxic than docetaxel ( < 0.001). Diabetes was also significantly associated with the development of TIPN. The candidate gene analysis showed no significant association between either SNP () and the development of TIPN overall, or severe TIPN. Meta-analysis showed no association between these two variants and TIPN. Transformed into combined CYP3A metaboliser phenotypes, 30 taxane recipients were poor metabolisers, 159 were intermediate metabolisers, and 22 were extensive metabolisers. No significant association was observed between metaboliser status and case-control status. We have shown that the risk of peripheral neuropathy during taxane chemotherapy is greater in patients who have diabetes. CYP3A genotype or phenotype was not identified as a risk factor in either the candidate gene analysis or the systematic review/meta-analysis, although we cannot exclude the possibility of a minor contribution, which would require a larger sample size.
PubMed: 37469869
DOI: 10.3389/fphar.2023.1178421 -
Journal of Ovarian Research Jul 2023Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis Review
Dose-dense regimen versus conventional three-weekly paclitaxel combination with carboplatin chemotherapy in first-line ovarian cancer treatment: a systematic review and meta-analysis.
BACKGROUND
Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer.
METHODS
An electronic search following PRISMA guidelines was conducted (Prospero registration number: CRD42020187622), and then a systematic review and meta-analysis of included literature were initiated to determine which regimen was better.
RESULTS
Four randomized controlled trials were included in the qualitative evaluation, and 3699 ovarian cancer patients were included in the meta-analysis. The meta-analysis revealed that the dose-dense regimen could prolong PFS (HR0.88, 95%CI 0.81-0.96; p = 0.002) and OS (HR0.90, 95%CI 0.81-1.02; p = 0.09), but it also increased the overall toxicity (OR = 1.102, 95%CI 0.864-1.405; p = 0.433), especially toxicity of anemia (OR = 1.924, 95%CI 1.548-2.391; p < 0.001), neutropenia (OR = 2.372, 95%CI 1.674-3.361; p < 0.001). Subgroup analysis indicated that the dose-dense regimen could significantly prolong not only PFS (HR0.76, 95%CI 0.63-0.92; p = 0.005 VS HR0.91, 95%CI 0.83-1.00; p = 0.046) but also OS (HR0.75, 95%CI 0.557-0.98; p = 0.037 VS HR0.94, 95%CI 0.83-1.07; p = 0.371) in Asian, and overall toxicity was significantly increased in Asians (OR = 1.28, 95%CI: 0.877-1.858, p = 0.202) compared to non-Asians (OR = 1.02, 95%CI 0.737-1.396, p = 0.929).
CONCLUSION
Paclitaxel dose-dense regimen could prolong PFS and OS, but it also increased the overall toxicity. Therapeutic benefits and toxicity of dose-dense are more obvious in Asians compared to non-Asians, which need to be further confirmed in clinical trials.
Topics: Humans; Female; Carboplatin; Paclitaxel; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Randomized Controlled Trials as Topic
PubMed: 37430376
DOI: 10.1186/s13048-023-01216-z -
Clinical Cardiology Aug 2023Drug-coated balloons (DCBs) have been used in dialysis patients with arteriovenous fistula (AVF) stenosis, but whether DCBs have advantages over ordinary balloons is... (Meta-Analysis)
Meta-Analysis Review
Drug-coated balloons (DCBs) have been used in dialysis patients with arteriovenous fistula (AVF) stenosis, but whether DCBs have advantages over ordinary balloons is still controversial. A meta-analysis was designed to investigate the safety and efficacy of DCBs and common balloons (CBs) in the treatment of AVF stenosis. We searched the PubMed, EMBASE, and China National Knowledge Internet (CNKI) databases for randomized controlled trials that evaluated the comparison of DCB angioplasty versus CB angioplasty for AVF stenosis in dialysis patients and reported at least one outcome of interest. The results showed that the DCB group had a higher first-stage patency rate of the target lesion 6 months [odds ratio, OR = 2.31, 95% confidence interval, CI: (1.69, 3.15), p < .01] and 12 months [OR = 2.09, 95% CI: (1.50, 2.91), p < .01] after surgery. There was no statistically significant difference in all-cause mortality between the two groups at 6 months [OR = 0.85, 95% CI: (0.47, 1.52), p = .58] and 12 months [OR = 0.99, 95% CI: (0.60, 1.64), p = .97]. Compared with CB, DCBs as a new endovascular treatment for AVF stenosis have a higher primary patency rate of target lesions and can delay the occurrence of restenosis. There is no evidence that DCB can increase the mortality of patients.
Topics: Humans; Vascular Patency; Graft Occlusion, Vascular; Constriction, Pathologic; Treatment Outcome; Coated Materials, Biocompatible; Time Factors; Angioplasty, Balloon; Arteriovenous Fistula; Paclitaxel
PubMed: 37417371
DOI: 10.1002/clc.24078 -
Frontiers in Pharmacology 2023In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have...
In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart's function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity. This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients' treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.
PubMed: 37383708
DOI: 10.3389/fphar.2023.1137983 -
Frontiers in Neuroscience 2023The prognosis for patients with ovarian cancer is bleak. Clinical trials have shown the efficacy of bevacizumab in ovarian cancer treatment. However, life-threatening...
BACKGROUND
The prognosis for patients with ovarian cancer is bleak. Clinical trials have shown the efficacy of bevacizumab in ovarian cancer treatment. However, life-threatening strokes may limit the usage of bevacizumab and require specific follow-up strategies. This study aims to systematically evaluate the risk of stroke of bevacizumab treatment in ovarian cancer.
METHODS
We retrieved all relevant articles published up to December 4th, 2022, from Embase, PubMed, Web of Science, and the Cochrane Library. The risk of stroke in patients with ovarian cancer treated with bevacizumab combined with chemotherapy was analyzed. Meta-analysis was performed using the Stata 17 software and R 4.2.1 program.
RESULTS
Six randomized controlled trials (RCTs) of bevacizumab combined with chemotherapy or chemotherapy for ovarian cancer and six single-experimental-arm trials were included in this study. The meta-analysis showed a pooled risk ratio (RR) of 2.14 [95% confidence interval (CI): 0.88-7.99] for patients with ovarian cancer treated with bevacizumab combined with chemotherapy. Subgroup analyses showed that the incidence of stroke-related adverse events in the carboplatin + paclitaxel + bevacizumab group was 0.01% (95% CI: 0.00-0.01, < 0.01). The incidence of stroke-related adverse events was 0.01% (95% CI: 0.00-0.01, < 0.01) in patients aged ≥60. The incidence of stroke caused by cerebral ischemia and cerebral hemorrhage was 0.01% (95% CI: 0.01-0.02, = 0.27) and 0.01% (95% CI: 0.00-0.01, < 0.01), respectively.
CONCLUSIONS
This meta-analysis indicates that chemotherapy combined with bevacizumab may not increase the incidence of stroke in patients with ovarian cancer. However, stroke-related adverse events may be higher in older patients. Cerebral hemorrhage might cause the incidence of stroke more than cerebral ischemia.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42022381003).
PubMed: 37360160
DOI: 10.3389/fnins.2023.1187957