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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2019

01-08-2019 | Breast Cancer | Review

Clinical benefit, toxicity and cost of metastatic breast cancer therapies: systematic review and meta-analysis

Authors: John Silberholz, Dimitris Bertsimas, Linda Vahdat

Published in: Breast Cancer Research and Treatment | Issue 3/2019

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Abstract

Purpose

Oncologists, clinical trialists, and guideline developers need tools that enable them to efficiently review the settings and results of previous studies testing metastatic breast cancer (MBC) drug therapies.

Methods

We searched the literature to identify clinical trials testing MBC drug therapies. Key eligibility criteria included at least 90% of patients enrolled in the trial having MBC, therapeutic clinical trials, and Phase II–III studies. Studies were stratified based on patients’ tumor receptor statuses and prior exposure to therapy. Survival and toxicity of each drug therapy were estimated from randomized controlled trials using network meta-analysis and from all studies using meta-analysis. These results, along with estimated drug costs, are presented in a web-based visualization tool.

Results

We included 1865 studies containing 2676 treatment arms and 184,563 patients in the tool (http://​www.​cancertrials.​info). Meta-analysis-based efficacy and toxicity estimates are available for 85 HER-2-directed therapies, 84 hormonal therapies, and 442 undirected therapies. Network meta-analysis-based estimates are available for 16 HER-2-directed therapies, 26 hormonal therapies, and 131 undirected therapies.

Conclusions

In this era of increasing choices of MBC therapeutic agents and no superior approach to choosing a treatment regimen, the ability to compare multiple therapies based on survival, toxicity and cost would enable treating physicians to optimize therapeutic choices for patients. For investigators, it can point them in research directions that were previously non-obvious and for guideline designers, enable them to efficiently review the MBC clinical trial literature and visualize how regimens compare in the key dimensions of clinical benefit, toxicity, and cost.
Appendix
Available only for authorised users
Footnotes
1
Assistance in the literature review and data extraction was provided by former MIT graduate students Allison O’Hair and Stephen Relyea and by MIT and Wellesley undergraduate students Emily Chen, Michael Chen, Shahrin Islam, Siva Nagarajan, David Sukhin, Pei Tao, Roza Trilesskaya, Victoria Wang, Mimi Williams, and Joanna Yeh.
 
Literature
1.
Schnipper L, Davidson N, Wollins D et al (2016) Updating the American Society of Clinical Oncology value framework: revisions and reflections in response to comments received. J Clin Oncol 34(24):2925–2934CrossRefPubMed
2.
3.
Ge L, Tang Y, Zhang Q et al (2017) A network meta-analysis on the efficacy of targeted agents in combination with chemotherapy for treatment of advanced/metastatic triple-negative breast cancer. Oncotarget 8(35):59539–59551PubMedPubMedCentral
4.
Wilson F, Varu A, Mitra D, Cameron C, Iyer S (2017) Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer. Breast Cancer Res Treat 166(1):167–177CrossRefPubMedPubMedCentral
5.
Leung HWC, Leung JH, Chan ALF (2018) Efficacy and safety of a combination of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer: a network meta-analysis. Expert Opin Drug Saf 17(1):1–7CrossRefPubMed
6.
Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13(3):176–181CrossRefPubMed
7.
Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analysis of the published literature for survival endpoints. Stat Med 17(24):2815–2834CrossRefPubMed
8.
Silberholz J (2015) Analytics for improved cancer screening and treatment. Dissertation, MIT
9.
Bertsimas D, O’Hair A, Relyea S, Silberholz J (2016) An analytics approach to designing combination chemotherapy regimens for cancer. Manage Sci 62(5):1511–1531CrossRef
10.
National Comprehensive Cancer Network (2016) NCCN clinical practice guidelines in oncology: breast cancer, version 2.2016
11.
12.
13.
Tibshirani R (1996) Regression shrinkage and selection via the lasso. J R Statist Soc B 58(1):267–288
14.
Rücker G, Schwarzer G (2014) Reduce dimension or reduce weights? Comparing two approaches to multi-arm studies in network meta-analysis. Stat Med 33(25):4353–4369CrossRefPubMed
15.
Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 379(22):2108–2121CrossRefPubMed
16.
Masuda N, Nishimura R, Takahashi M et al (2018) Palbociclib in combination with letrozole as first-line treatment for advanced breast cancer: A Japanese phase II study. Cancer Sci 109(3):803–813CrossRefPubMedPubMedCentral
17.
Finn R, Crown J, Lang I et al (2015) The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16(1):25–35CrossRefPubMed
18.
Finn R, Martin M, Rugo H et al (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375(20):1925–1936CrossRefPubMed
19.
Hess D, Köberle D, Thürlimann B et al (2007) Capecitabine and vinorelbine as first-line treatment in elderly patients (≥ 65 years) with metastatic breast cancer: a phase II trial (SAKK 25/99). Oncology 73(3–4):228–237CrossRefPubMed
20.
Smorenburg CH, de Groot SM, van Leeuwen-Stok AE et al (2014) A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG. Ann Oncol 25(3):599–605CrossRefPubMedPubMedCentral
21.
Easterbrook PJ, Gopalan R, Berlin JA, Matthews DR (1991) Publication bias in clinical research. Lancet 337(8746):867–872CrossRefPubMed
Metadata
Title
Clinical benefit, toxicity and cost of metastatic breast cancer therapies: systematic review and meta-analysis
Authors
John Silberholz
Dimitris Bertsimas
Linda Vahdat
Publication date
01-08-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05208-w

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