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Baseline characteristics and first-line treatment patterns in patients with HER2-positive metastatic breast cancer in the SystHERs registry

Abstract

Background

Systemic Therapies for HER2-Positive Metastatic Breast Cancer Study (SystHERs, NCT01615068) was a prospective, observational disease registry designed to identify treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer (MBC) in real-world treatment settings.

Methods

SystHERs enrolled patients aged ≥ 18 years with recently diagnosed HER2-positive MBC. Treatment regimens and clinical management were determined by the treating physician. In this analysis, patients were compared descriptively by first-line treatment, age, or race. Multivariate logistic regression was used to examine the associations between baseline variables and treatment selections. Clinical outcomes were assessed in patients treated with trastuzumab (Herceptin [H]) + pertuzumab (Perjeta [P]).

Results

Patients were enrolled from June 2012 to June 2016. As of February 22, 2018, 948 patients from 135 US treatment sites had received first-line treatment, including HP (n = 711), H without P (n = 175), or no H (n = 62) (with or without chemotherapy and/or hormonal therapy). Overall, 68.7% received HP + taxane and 9.3% received H without P + taxane. Patients aged < 50 years received HP (versus H without P) more commonly than those ≥ 70 years (odds ratio 4.20; 95% CI, 1.62–10.89). Chemotherapy was less common in patients ≥ 70 years (68.2%) versus those < 50 years (88.0%) or 50–69 years (87.4%). Patients treated with HP had median overall survival of 53.8 months and median progression-free survival of 15.8 months.

Conclusions

Our analysis of real-world data shows that most patients with HER2-positive MBC received first-line treatment with HP + taxane. However, older patients were less likely to receive dual HER2-targeted therapy and chemotherapy.

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Data availability

Qualified researchers may request access to de-identified patient level data through the Clinical Study Data Request platform (www.clinicalstudydatarequest.com) and will be provided with accompanying clinical study documentation (protocol and any associated amendments, annotated case report form, reporting and analysis plan, dataset specifications, and the clinical study report). Researchers requesting access to clinical study documentation only can do so via the following link: http://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing/clinical_study_documents_request_form.htm. Documents are made available on application, per scope and timing criteria as published on the Clinical Study Data Request platform.

Abbreviations

CI:

Confidence interval

CVD:

Cardiovascular disease

ECOG:

Eastern Cooperative Oncology Group

FDA:

Food and Drug Administration

H:

Trastuzumab

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

IRB:

Institutional review board

MBC:

Metastatic breast cancer

OR:

Odds ratio

OS:

Overall survival

P:

Pertuzumab

PFS:

Progression-free survival

SEER:

Surveillance, Epidemiology, and End Results

SystHERs:

Systemic Therapies for HER2-Positive Metastatic Breast Cancer Study

T-DM1:

Trastuzumab emtansine

US:

United States

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Acknowledgements

The authors are grateful to the patients, families, and investigators who participated in SystHERs. The authors thank Musa Mayer for her work as part of the SystHERs Steering Committee; the entire SystHERs team, including clinical operations leads Michelle Usher (F. Hoffmann-La Roche/Genentech, Inc.) and Sandy Lam (F. Hoffmann-La Roche/Genentech, Inc.); Bongin Yoo (F. Hoffmann-La Roche/Genentech, Inc.) for his contributions to the statistical analysis; Allen Lee (Everest Clinical Research Services, Inc.) for his assistance with the statistical analysis; and Bokai Xia (F. Hoffmann-La Roche/Genentech, Inc.) for his statistical programming expertise. Third-party writing assistance was provided by Meredith Kalish, MD, of Ashfield Healthcare Communications, part of UDG Healthcare plc, and funded by Genentech, Inc. F. Hoffmann-La Roche/Genentech, Inc. funded the SystHERs study and participated in the study design, data collection, data analysis, data interpretation, and writing of this report.

Funding

This study was funded by F. Hoffmann-La Roche/Genentech.

Author information

Affiliations

Authors

Contributions

All authors contributed to the study conception, design, oversight, and data interpretation. Statistical analysis was performed by HL. The first draft of the manuscript was written by PAK and all authors participated in revisions on subsequent versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Peter A. Kaufman.

Ethics declarations

Conflict of interest

P.A. Kaufman has received consulting fees and research funding from F. Hoffmann-La Roche/Genentech, Lilly, Celgene, Eisai, Amgen, Novartis, Macrogenics, and Puma Biotechnology. S.A. Hurvitz has received travel support from Novartis, Lilly, and OBI Pharma; and research funding from F. Hoffmann-La Roche/Genentech, Novartis, GlaxoSmithKline, Boehringer Ingelheim, Sanofi, Pfizer, Amgen, OBI Pharma, Puma Biotechnology, Dignitana, Bayer, BioMarin, Lilly, Merrimack, Daiichi-Sankyo, Immunomedics, Macrogenics, Pieris, and Seattle Genetics. J. O’Shaughnessy has received consulting fees from AbbVie Inc., Agendia, Amgen Biotechnology, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Eisai, Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeutics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, Pfizer, Puma Biotechnology, Roche, Seattle Genetics, and Syndax Pharmaceuticals. G. Mason has no additional disclosures. D.A. Yardley has received consulting/advisory fees from Novartis and Genentech; and research funding from F. Hoffmann-La Roche/Genentech and Novartis. A. Brufsky has received consulting fees and travel support from F. Hoffmann-La Roche/Genentech, Novartis, Pfizer, Sandoz, AstraZeneca, Amgen, and Lilly. H.S. Rugo has received travel support from Merck, Mylan, Puma, Lilly, and Pfizer; and research funding from F. Hoffmann-La Roche/Genentech, Pfizer, Novartis, Lilly, OBI Pharma, Macrogenics, and Merck. M. Cobleigh has received consulting fees and research funding from F. Hoffmann-La Roche/Genentech. S.M. Swain has received consulting fees from AstraZeneca, Athenex, Daiichi-Sanyo, Eli Lilly and Company, F. Hoffmann-La Roche/Genentech, Genomic Health, Inivata, Ltd., Molecular Therapeutics, Novartis, Pieris Pharmaceuticals, Silverback Therapeutics, and Tocagen; research funding from F. Hoffmann-La Roche/Genentech and Kailos Genetics; non-financial support from Athenex, Daiichi-Sanyo, Eli Lilly and Company, F. Hoffmann-La Roche/Genentech, Inivata, Ltd., Novartis, Pieris Pharmaceuticals, Caris Life Sciences, AstraZeneca, Bristol-Myers Squibb; and is on an Independent Data Monitoring Committee for AstraZeneca. D. Tripathy has received consulting fees from Pfizer and Novartis, and research funding from Novartis. A. Morris was a contract employee of Genentech. V. Antao is an employee of Genentech and owns stock in F. Hoffmann-La Roche/Genentech. H. Li is an employee of F. Hoffmann-La Roche/Genentech. M. Jahanzeb has received consulting fees from F. Hoffmann-La Roche/Genentech, and served on a Scientific Advisory Board and Data and Safety Monitoring Board for Puma. All authors received non-financial support from F. Hoffmann-La Roche in the form of medical writing support for this manuscript.

Ethical approval

SystHERs was conducted in accordance with US Food and Drug Administration regulations, the International Conference on Harmonisation E6 Guidelines for Good Clinical Practice, the Declaration of Helsinki, and applicable local laws. Each participating site obtained approval of the study protocol by the site’s ethics committee or institutional review board (IRB), or a central IRB for sites that did not have an IRB.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Kaufman, P.A., Hurvitz, S.A., O’Shaughnessy, J. et al. Baseline characteristics and first-line treatment patterns in patients with HER2-positive metastatic breast cancer in the SystHERs registry. Breast Cancer Res Treat 188, 179–190 (2021). https://doi.org/10.1007/s10549-021-06103-z

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Keywords

  • HER2-positive
  • Metastatic breast cancer
  • SystHERs
  • Baseline characteristics
  • First-line treatment patterns