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      Comparison between nab-paclitaxel and solvent-based taxanes as neoadjuvant therapy in breast cancer: a systematic review and meta-analysis

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          Abstract

          Background

          To compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer.

          Methods

          We systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019.

          Results

          The primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27–1.83, P < 0.001; ypT0/is ypN0: OR = 1.40, 95%CI: 1.17–1.68, P < 0.001). The benefits of nab-paclitaxel on pCR were persistent in HER2-negative, hormone receptor (HR)-positive breast cancer (OR = 1.53, 95%CI: 1.07–2.19, P = 0.020), triple-negative breast cancer (weekly/every 2 weeks regimen; OR = 2.95, 95%CI: 1.54–5.67, P < 0.001), and tumors with Ki-67 > 20% (OR = 1.63, 95%CI: 1.26–2.12, P < 0.001). Patients treated with nab-paclitaxel had better event-free survival (EFS; HR = 0.69, 95%CI: 0.57–0.85, P < 0.001) than with sb-taxanes. There were no differences in most of grade  > 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11–0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37–3.23, P = 0.001) and grade  > 3 (OR = 4.01, 95%CI: 2.51–6.41, P < 0.001) neuropathy.

          Conclusion

          Nab-paclitaxel is effective for the treatment of non-metastatic breast cancer in the neoadjuvant setting. Nab-paclitaxel could improve pCR rate and EFS compared with sb-taxanes and with reasonable toxicities.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12885-021-07831-7.

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          Most cited references44

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          Measuring inconsistency in meta-analyses.

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            The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

            Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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              Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.

              Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS. We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response--ypT0 ypN0, ypT0/is ypN0, and ypT0/is--for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS. We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39-0·51; ypT0/is ypN0: 0·48, 0·43-0·54) and OS (0·36, 0·30-0·44; 0·36, 0·31-0·42) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 0·60, 95% CI 0·55-0·66; OS 0·51, 0·45-0·58). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 0·24, 95% CI 0·18-0·33; OS: 0·16, 0·11-0·25) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 0·15, 0·09-0·27; OS: 0·08, 0·03, 0·22). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=0·03, 95% CI 0·00-0·25) and OS (R(2)=0·24, 0·00-0·70). Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS. US Food and Drug Administration. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                liumiao@pkuph.edu.cn
                dr.liusiyao@pku.edu.cn
                706642668@qq.com
                shuwang@pkuph.edu.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                4 February 2021
                4 February 2021
                2021
                : 21
                : 118
                Affiliations
                GRID grid.411634.5, ISNI 0000 0004 0632 4559, Breast Center, , Peking University People’s Hospital, ; Beijing, China
                Article
                7831
                10.1186/s12885-021-07831-7
                7863369
                33541289
                6a73a485-b4fc-4aa5-b134-01f0e1a6bb4a
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 2 May 2020
                : 24 January 2021
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                breast cancer,neoadjuvant chemotherapy,paclitaxel,albumin-bound paclitaxel,meta-analysis

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