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Triple negative breast cancer and platinum-based systemic treatment: a meta-analysis and systematic review.
Pandy, JGP, Balolong-Garcia, JC, Cruz-Ordinario, MVB, Que, FVF
BMC cancer. 2019;(1):1065
Abstract
BACKGROUND Triple negative breast cancer (TNBC) represents 15-20% of breast cancers. Due to its heterogeneity and high rates of relapse, there is a need to optimize treatment efficacy. Platinum chemotherapy is still controversial and currently not recommended as first-line treatment for TNBC. Recent studies have shown promising activity of this regimen. This study was done to evaluate the effect of platinum chemotherapy on pathologic complete response (pCR) after neoadjuvant treatment for early TNBC and progression-free survival (PFS) in metastatic TNBC. METHODS A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were done to identify randomized controlled trials (RCTs) investigating the use of platinum-based chemotherapy in adults with TNBC. Studies were appraised using the Cochrane Collaboration tool. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) for pCR, and Hazard Ratios (HRs) with 95%CI for PFS were analyzed. RESULTS Eleven RCTs were included (N = 2946). Platinum-based chemotherapy showed pCR benefit of 40%vs27% (OR1.75,95% CI 1.46-2.62,p < 0.0001) in the neo-adjuvant setting. Subgroup analysis showed increased pCR rates (44.6%vs27.8%) with platinum plus taxane regimen (p < 0.0001). In metastatic TNBC, three RCTs were analyzed (N = 531), platinum treatment did not show PFS advantage (HR1.16,95%CI 0.90-1.49,p = 0.24). CONCLUSION Platinum chemotherapy is associated with increased pCR rates in TNBC, hence it is a viable option for patients in the neoadjuvant setting. Subgroup analysis showed that the combination of platinum and taxanes (Carboplatin/Paclitaxel) improved pCR. However, no PFS advantage was seen in metastatic TNBC. Given the current conflicting data in metastatic TNBC, further exploration with additional powered studies is needed.
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Influence of the ABCB1 polymorphisms on the response to Taxane-containing chemotherapy: a systematic review and meta-analysis.
Jiang, Q, Xu, M, Liu, Y, Chen, Y, Feng, J, Wang, X, Liang, S, Li, D, Yang, X
Cancer chemotherapy and pharmacology. 2018;(2):315-323
Abstract
PURPOSE Multidrug resistance mediated by ABCB1 has been perceived to be one of the obstacles for cancer chemotherapy. This meta-analysis was performed to verify the effect of the ABCB1 rs1045642 and rs1128503 polymorphisms on the response to Taxane-containing chemotherapy. METHODS Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of these two ABCB1 polymorphisms. R scripts were developed to perform the meta-analysis. RESULTS A total of nine articles (including nine studies for rs1045642 and five for rs1128503) were collected in our systematic review. However, our meta-analysis showed no significant effect of these two ABCB1 polymorphisms on the response to Taxane-containing regimens. CONCLUSIONS This study highlights the unsuitability of relying on the ABCB1 rs1045642 and rs1128503 polymorphisms as therapeutic response biomarkers of Taxane-containing chemotherapy. Further polycentric studies in larger and multiracial populations are needed to validate the conclusions.
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Taxane-containing regimens for metastatic breast cancer.
Ghersi, D, Willson, ML, Chan, MM, Simes, J, Donoghue, E, Wilcken, N
The Cochrane database of systematic reviews. 2015;(6):CD003366
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Abstract
BACKGROUND It is generally accepted that taxanes are among the most active chemotherapy agents in the management of metastatic breast cancer. This is an update of a Cochrane review first published in 2003. OBJECTIVES The objective of this review was to compare taxane-containing chemotherapy regimens with regimens not containing a taxane in the management of women with metastatic breast cancer. SEARCH METHODS In this review update, we searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 14 February 2013 using keywords such as 'advanced breast cancer' and 'chemotherapy'. We searched reference lists of articles, contacted study authors, and did not apply any language restrictions. SELECTION CRITERIA Randomised controlled trials comparing taxane-containing chemotherapy regimens to regimens without taxanes in women with metastatic breast cancer. We included published and unpublished studies. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. We derived hazard ratios (HRs) for overall survival, time to progression, and time to treatment failure where possible, and used a fixed-effect model for meta-analysis. We represented objective tumour response rates and toxicity as risk ratios (RRs). We extracted quality of life data where present. MAIN RESULTS This review included 28 studies. The updated analysis included 6871 randomised women, while the original review had 3643 women. Of the 28 included studies, we considered 19 studies to be at low risk of bias overall; however, some studies failed to report details on allocation concealment and methods of outcome assessment for those outcomes that are more likely to be influenced by a lack of blinding (for example tumour response rate). Studies varied in the taxane-containing chemotherapy backbone, and the comparator arms and were categorised into three groups: Regimen A plus taxane versus Regimen A (2 studies); Regimen A plus taxane versus Regimen B (14 studies); and single-agent taxane versus Regimen C (13 studies). Thirteen studies used paclitaxel, 14 studies used docetaxel, and 1 study allowed the investigator to decide on the type of taxane; the majority of studies delivered a taxane every 3 weeks. Twenty studies administered taxanes as first-line treatment, and 21 studies involved anthracycline naïve women in the metastatic setting. The combined HR for overall survival and time to progression favoured the taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.88 to 0.99, P = 0.002, deaths = 4477; and HR 0.92, 95% CI 0.87 to 0.97, P = 0.002, estimated 5122 events, respectively) with moderate to substantial heterogeneity across trials. If the analyses were restricted to studies of first-line chemotherapy, this effect persisted for overall survival (HR 0.93, 95% CI 0.87 to 0.99, P = 0.03) but not for time to progression (HR 0.96, 95% CI 0.90 to 1.02, P = 0.22). Tumour response rates appeared to be better with taxane-containing chemotherapy in assessable women (RR 1.20, 95% CI 1.14 to 1.27, P < 0.00001) with substantial heterogeneity across studies. Taxanes were associated with an increased risk of neurotoxicity (RR 4.84, 95% CI 3.18 to 7.35, P < 0.00001, 24 studies) and hair loss (RR 2.37, 95% CI 1.45 to 3.87, P = 0.0006, 11 studies) but less nausea/vomiting compared to non-taxane-containing regimens (RR 0.62, 95% CI 0.46 to 0.83, P = 0.001, 26 studies). Leukopaenia and treatment-related death did not differ between the two groups (RR 1.07, 95% CI 0.97 to 1.17, P = 0.16, 28 studies; and RR 1.00, 95% CI 0.63 to 1.57, P = 0.99, 23 studies, respectively). For quality of life measures, none of the individual studies reported a difference in overall or any of quality of life subscales between taxane-containing and non-taxane chemotherapy regimens. AUTHORS' CONCLUSIONS Taxane-containing regimens appear to improve overall survival, time to progression, and tumour response rate in women with metastatic breast cancer. Taxanes are also associated with an increased risk of neurotoxicity but less nausea and vomiting compared to non-taxane-containing regimens. The considerable heterogeneity encountered across studies probably reflects the varying efficacy of the comparator regimens used in these studies and indicates that taxane-containing regimens are more effective than some, but not all, non-taxane-containing regimens.
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Benefit of taxanes as adjuvant chemotherapy for early breast cancer: pooled analysis of 15,500 patients.
Bria, E, Nistico, C, Cuppone, F, Carlini, P, Ciccarese, M, Milella, M, Natoli, G, Terzoli, E, Cognetti, F, Giannarelli, D
Cancer. 2006;(11):2337-44
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Abstract
BACKGROUND The magnitude of the survival benefit of taxanes as adjuvant chemotherapy for early breast cancer is still unclear. A pooled analysis of Phase III trials was performed to assess the advantages that adjuvant taxane chemotherapy has over standard chemotherapy. METHODS All Phase III trials were considered eligible. A pooled analysis was accomplished and event-based relative risk ratios (RR) with 95% confidence intervals (95% CI) were derived. The significant differences in disease-free survival (DFS) and overall survival (OS) were explored. Magnitude outcome measures were absolute benefits and the number of patients needed to treat. A heterogeneity test was applied as well. A sensitivity analysis in 6 subpopulations was also performed. RESULTS Nine trials designed to assess if paclitaxel or docetaxel improve survival (15,598 patients) were gathered. One of the 9 trials did not report OS results. Significant differences in favor of taxanes were seen in DFS in the overall (RR: 0.86; 95% CI, 0.81-0.90 [P<.00001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.79-0.89 [P<.0001]), and in OS in the overall (RR: 0.87; 95% CI, 0.81-0.83 [P<.0001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.77-0.92 [P<.0001]). The absolute benefits in DFS and OS in favor of taxanes ranged from 3.3% to 4.6% and from 2.0% to 2.8%, respectively. CONCLUSIONS Considering all the available Phase III trials, taxane-based adjuvant chemotherapy for early breast cancer seems to add a significant benefit in both DFS and OS over standard chemotherapy. The lack of significant heterogeneity in the sensitivity analysis underscores the homogeneous effect across all trials.
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Taxane containing regimens for metastatic breast cancer.
Ghersi, D, Wilcken, N, Simes, J, Donoghue, E
The Cochrane database of systematic reviews. 2005;(2):CD003366
Abstract
BACKGROUND It is generally accepted that taxanes are among the most active chemotherapy agents in the management of metastatic breast cancer. OBJECTIVES To identify and review the randomised evidence comparing taxane containing chemotherapy regimens with regimens not containing a taxane in the management of women with metastatic breast cancer. SEARCH STRATEGY The specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library. SELECTION CRITERIA Randomised trials comparing taxane-containing chemotherapy regimens with regimens not containing taxanes in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS Data were collected from published trials. Studies were assessed for eligibility and quality, and data were extracted, by two independent reviewers. Hazard ratios were derived for time-to-event outcomes where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present. MAIN RESULTS Twenty one eligible trials were identified of which 12 have published time-to-event data and 16 have reported response data. The quality of randomisation was generally not described. An estimated 2621 deaths in 3643 randomised women demonstrate a statistically significant difference in favour of taxane-containing regimens with a HR for overall survival of 0.93 (95% CI=0.86-1.00, p=0.05) and no statistically significant heterogeneity. If the analysis is restricted to trials of firstline chemotherapy the HR changes to 0.92 and is no longer statistically significant (95% CI 0.84-1.02, p=0.11). There was also a significant difference in favour of taxanes in relation to time to progression (overall HR 0.92, 95%CI 0.85-0.99, p=0.02) and overall response in assessable women (overall OR 1.34, 95%CI 1.18-1.52, p<0.00001) however there was strong statistical evidence of heterogeneity (P<0.00001), probably reflecting the varying efficacy of the comparator regimens used in the trials. AUTHORS' CONCLUSIONS When all trials are considered, taxane-containing regimens appear to improve overall survival, time to progression and overall response in women with metastatic breast cancer. The degree of heterogeneity encountered indicates that taxane-containing regimens are more effective than some, but not all non-taxane-containing regimens.
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Docetaxel administration schedule: from fever to tears? A review of randomised studies.
Engels, FK, Verweij, J
European journal of cancer (Oxford, England : 1990). 2005;(8):1117-26
Abstract
The anti-cancer agent docetaxel is approved for the treatment of patients with locally advanced or metastatic breast cancer, non-small cell lung cancer (NSCLC) and for the treatment of androgen-independent prostate cancer. At the recommended dose of 60-100 mg/m2 given every 3 weeks, severe neutropenia is the dose-limiting toxicity and a major concern especially when treating patients at high-risk from myelotoxic complications. A less toxic schedule, involving weekly docetaxel administration was developed for patients with poor performance status, multiple comorbidities, poor haematological reserves or those who were heavily pre-treated, elderly or patients for whom palliation is the focus of treatment. Recent randomised trials allow a comparison of efficacy and toxicity between weekly and 3-weekly treatments. Efficacy appears to be similar for the two schedules regardless of the disease while weekly docetaxel is significantly less myelotoxic. However, this benefit comes at the cost of cumulative increases in hyperlacrimation, skin- and nail-toxicity and negatively affects quality of life. Currently, 3-weekly docetaxel remains the standard schedule for treatment, whereas the weekly schedule offers a possibility of treatment individualisation for those patients where the risk of myelosuppression is considered unacceptable.