Dataset Information

Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients.

ABSTRACT:

Background

Taxanes have been extensively used as adjuvant chemotherapy for the treatment of early or operable breast cancer, particularly in high risk, node-negative breast cancer. Previous studies, however, have reported inconsistent findings regarding their clinical efficacy and safety. We investigated disease-free survival (DFS), overall survival (OS), and drug-related toxicities of taxanes by a systematic review and meta-analysis.

Methodology and principal findings

We systematically searched PubMed, EMBASE, the Cochrane Center Register of Controlled Trials, proceedings of major meetings, and reference lists of articles for studies conducted between January 1980 and April 2011. Randomized controlled trials (RCTs) comparing chemotherapy with and without taxanes in the treatment of patients with early-stage or operable breast cancer were eligible for inclusion in our analysis. The primary endpoint was DFS. Nineteen RCTs including 30698 patients were identified, including 8426 recurrence events and 3803 deaths. Taxanes administration yielded a 17% reduction of hazard ratio (HR) for DFS (HR?=?0.83, 95% CI 0.79-0.88, p<0.001) and a 17% reduction of HR for OS (HR?=?0.83, 95% CI 0.77-0.90, p<0.001). For high risk, node-negative breast cancer, the pooled HR also favoured the taxane-based treatment arm over the taxane-free treatment arm (HR?=?0.82, 95% CI 0.77-0.87, p?=?0.022). A significantly increased rate of neutropenia, febrile neutropenia, fatigue, diarrhea, stomatitis, and oedema was observed in the taxane-based treatment arm.

Conclusions/significance

Adjuvant chemotherapy with taxanes could reduce the risk of cancer recurrence and death in patients with early or operable breast cancer, although the drug-related toxicities should be balanced. Furthermore, we also demonstrated that patients with high risk, node-negative breast cancer also benefited from taxanes therapy, a result that was not observed in previous studies.

SUBMITTER: Qin YY

PROVIDER: S-EPMC3206064 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients.

Qin Ying-Yi YY Li Hui H Guo Xiao-Jing XJ Ye Xiao-Fei XF Wei Xin X Zhou Yu-Hao YH Zhang Xin-Ji XJ Wang Chao C Qian Wei W Lu Jian J He Jia J

PloS one 20111101 11

<h4>Background</h4>Taxanes have been extensively used as adjuvant chemotherapy for the treatment of early or operable breast cancer, particularly in high risk, node-negative breast cancer. Previous studies, however, have reported inconsistent findings regarding their clinical efficacy and safety. We investigated disease-free survival (DFS), overall survival (OS), and drug-related toxicities of taxanes by a systematic review and meta-analysis.<h4>Methodology and principal findings</h4>We systemat ...[more]

PMID: 22069477

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Project description:BackgroundResearchers have demonstrated that the combined use of taxanes and chemotherapy drugs, especially paclitaxel-based treatment, appeared to clinically benefit on advanced triple negative breast cancer (TNBC). This meta-analysis aims to obtain the existent evidence on efficacy and safety for taxanes-based combination therapy to treat advanced TNBC.MethodsFrom 1991 to June 2022, seven databases (PubMed, Web of Science, Cochrane Library, Embase VIP, Wanfang, and CNKI databases) were comprehensively searched with no restricted language and region. The included randomized controlled trials (RCTs) compared taxanes-based combination therapy versus taxanes or other chemotherapy drugs. Statistical analysis was conducted using random-effect model, and the quality of RCTs was assessed using the tool of Cochrane Collaboration risk of bias.ResultsTwenty-six RCTs with a total of 8,236 advanced TNBC patients were included. Compared with taxanes monotherapy, taxanes-based combination therapy significantly prolonged progression-free survival (HR=0.79, 95%CI=0.74-0.83, I2= 0.0%, p=0.000) and overall survival (HR=0.88, 95%CI=0.82-0.94, I2= 9.3%, p=0.000) and increased the risk of vomiting (RR=1.26, 95%CI=1.07-1.48) and diarrhea (RR=1.82, 95%CI=1.22-2.70, I2= 90.3%, p=0.003). No statistical differences were observed in complete response rate (CRR), objective response rate (ORR), disease control rate (DCR), and progressive disease (PD) indexes (CRR: RR=1.38, 95%CI=0.96-1.99; ORR: RR=1.20, 95%CI=0.73-1.98; DCR: RR=1.09, 95%CI=1.00-1.19; PD: RR=0.70, 95%CI=0.47-1.04). Compared with other chemotherapy drugs, taxanes plus other chemotherapy drugs significantly reduced the incidence of vomiting (RR=0.60, 95%CI=0.44-0.84, I2= 12.3%, p=0.002) and neutropenia (RR=0.58, 95%CI=0.35-0.96, I2= 73.0%, p=0.036) during the treatment period.ConclusionsTaxanes-based combination therapy is evidently effective and well-tolerated in advanced TNBC, indicating that it might be a recommended option for treating advanced TNBC patients to some extent.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022337802.

Project description:BackgroundMany randomised controlled trials have investigated the effect of adjuvant chemotherapy in operable non-small-cell lung cancer. We undertook two comprehensive systematic reviews and meta-analyses to establish the effects of adding adjuvant chemotherapy to surgery, or to surgery plus radiotherapy.MethodsWe included randomised trials, not confounded by additional therapeutic differences between the two groups and that started randomisation on or after Jan 1, 1965, which compared surgery plus adjuvant chemotherapy versus surgery alone, or surgery plus adjuvant radiotherapy and chemotherapy versus surgery plus adjuvant radiotherapy. Updated individual patient data were collected, checked, and included in meta-analyses stratified by trial. The primary endpoint was overall survival, defined as time from randomisation until death by any cause. All analyses were by intention to treat.FindingsThe first meta-analysis of surgery plus chemotherapy versus surgery alone was based on 34 trial comparisons and 8447 patients (3323 deaths). We recorded a benefit of adding chemotherapy after surgery (hazard ratio [HR] 0.86, 95% CI 0.81-0.92, p<0.0001), with an absolute increase in survival of 4% (95% CI 3-6) at 5 years (from 60% to 64%). The second meta-analysis of surgery plus radiotherapy and chemotherapy versus surgery plus radiotherapy was based on 13 trial comparisons and 2660 patients (1909 deaths). We recorded a benefit of adding chemotherapy to surgery plus radiotherapy (HR 0.88, 95% CI 0.81-0.97, p=0.009), representing an absolute improvement in survival of 4% (95% CI 1-8) at 5 years (from 29% to 33%). In both meta-analyses we noted little variation in effect according to the type of chemotherapy, other trial characteristics, or patient subgroup.InterpretationThe addition of adjuvant chemotherapy after surgery for patients with operable non-small-cell lung cancer improves survival, irrespective of whether chemotherapy was adjuvant to surgery alone or adjuvant to surgery plus radiotherapy.FundingUK Medical Research Council, Institut Gustave-Roussy, Programme Hospitalier de Recherche Clinique (AOM 05 209), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

Project description:BackgroundDe-escalating anthracycline is gaining popularity for breast cancer patients. We aim to evaluate the non-inferiority of an anthracycline-free or short-term regimen to the standard anthracycline-based regimen for operable patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer.MethodsIt is a prospective, open-label, phase 3, randomized non-inferiority trial from June 1, 2010 to June 1, 2017. Follow-up had been kept until July 2019. This trial was conducted at Fudan University Shanghai Cancer Center. Patients with pT1-3N+ or pT2-3N0 but high-risk (grade II/III, lymphovascular invasion, ≤35 years of age or hormone-receptor negative) HER2-negative operable breast cancer were eligible and stratified by age, pathological tumour stage, pathological node status and hormone-receptor status. Patients were randomized to 6 cycles of docetaxel and cyclophosphamide (TC, n = 524), 3 cycles of cyclophosphamide/epirubicin/fluorouracil followed by 3 cycles of docetaxel (CEF-T, n = 523) or epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks (EC-P, n = 524) as the intention-to-treat population. Of these patients, 94% completed allocated therapy. Difference in disease-free survival (DFS) compared to EC-P. The prespecified non-inferiority margin was 4.5%, corresponding to the hazard ratio (HR) of 1.44 (one-sided α = 0.05), with an assumed 5-year DFS of 89% for EC-P.FindingsIncluded in the intention-to-treat population were 1571 patients (median [IQR] age, 50 [45-57] years; 92% estrogen receptor [ER]-positive; 59% pN+). Through a median follow-up of 5.5 years, HR for TC versus EC-P was 1.05 (5-year DFS: 85.0% vs. 85.9%; 90% confidence interval [CI]: 0.79-1.39, non-inferior P = 0.048) and for CEF-T versus EC-P, 0.99 (5-year DFS: 85.1% vs. 85.9%; 90% CI: 0.75-1.30, non-inferior P = 0.045). Grade 3 or 4 adverse events for TC included rash (3.9%) and peripheral neuropathy (2.8%) and for CEF-T and EC-P diarrhea and nausea/vomiting were predominant. Results of per-protocol analyses were similar.InterpretationBoth TC and CEF-T are non-inferior adjuvant regimen to EC-P mainly in patients with ER+HER2- breast cancer. TC is a safe regimen that avoids anthracycline-related side effects.FundingThis work was supported by grants from the National Natural Science Foundation of China (Grants 81672600, 81722032, 82072916, and 91959207), the 2018 Shanghai Youth Excellent Academic Leader, the Fudan ZHUOSHI Project, the Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (grant SHDC12010116), the Cooperation Project of Conquering Major Diseases in the Shanghai Municipality Health System (grant 2013ZYJB0302), the Innovation Team of the Ministry of Education (grant IRT1223), and the Shanghai Key Laboratory of Breast Cancer (grant 12DZ2260100) and the National Cancer Institute (grant P30 CA16058).

Project description:BackgroundNeoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials.MethodsWe obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality).FindingsPatients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45).InterpretationTumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.FundingCancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.

Project description:BackgroundThe absolute and relative benefits of adjuvant bisphosphonates on disease-free survival and overall survival in patients receiving contemporary systemic therapy for early breast cancer is uncertain.MethodsData from randomized trials of adjuvant bisphosphonates that recruited patients exclusively after 2000 and reported disease free survival and overall survival was utilized. Five-year disease-free survival and overall survival in bisphosphonates and control group along with associated hazard ratios were extracted. Absolute data were weighted by sample size and hazard ratios were pooled using inverse variance and random effects modelling. Meta-regression comprising linear regression weighted by sample size (mixed effects) was performed to explore association between disease and treatment related factors and absolute differences in benefit from bisphosphonates.ResultsEleven trials comprising 24023 patients were included in the analysis. For disease free survival, pooled hazard ratio was 0.89 (0.81-0.97, p = 0.008) with a 1.5 % weighted mean difference favoring bisphosphonates over control. There was no significant overall survival benefit (0.92, 0.82-1.03, p = 0.16). Among patients receiving anthracycline and taxane based chemotherapy, there were no differences in either disease free survival (0.95, 0.80-1.12) or overall survival (1.04, 0.81-1.32). Meta-regression showed lower benefits in higher risk patients (node-positive, larger tumor size, estrogen receptor-, grade 3 or those receiving chemotherapy). Overall, 1 % (95 % CI 0.75-1.15) of patients experienced osteonecrosis of jaw related to zoledronic acid.ConclusionsCompared to the Early Breast Cancer Trialist's Collaborative Group meta-analysis, benefit from adjuvant bisphosphonates is lower in recent trials especially in higher risk patients receiving contemporary chemotherapy. The balance between benefits and risks of adjuvant bisphosphonates should be considered in individual patients.

Dataset Information

Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients.

Background

Methodology and principal findings

Conclusions/significance

Publications

Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients.

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