Current and future landscape of targeted therapy in HER2-positive advanced breast cancer: redrawing the lines

Therapeutic Advances in Medical Oncology

卷:14

Systematic Review

Daniel Rayson¹  Anil Abraham Joy²  Jan-Willem Henning³  Julie Lemieux⁴  Heather McArthur⁵  Paul B. Card⁶  Rebecca Dent⁷  Christine Brezden-Masley⁸ 

[1] Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada

[2] Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada

[3] Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada

[4] Kaleidoscope Strategic, Inc., Toronto, ON, Canada

[5] Centre hospitalier universitaire de Québec, Université Laval, Quebec, QC, Canada

[6] National Cancer Centre Singapore, Duke-NUS Medical School, Singapore

[7] Cedars-Sinai Medical Center, Los Angeles, CA, USA

[8] Sinai Health, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

关键词: advanced disease;    breast cancer;    HER2-positive;    neratinib;    pertuzumab;    T-DM1;    T-DXd;    trastuzumab;    tucatinib;   

DOI  :  10.1177/17588359211066677

 received in 2021-08-27, accepted in 2021-11-26,  发布年份 2022

来源: Sage Journals

【 摘 要 】

Background:Evidence to date supports continued human epidermal growth factor receptor 2 (HER2) suppression beyond progression on HER2-directed therapy for advanced HER2-positive breast cancer. Data from several phase II and III trials evaluating HER2-directed therapy following second-line T-DM1 have recently become available.Methods:We performed a systematic search of the published and presented literature to identify phase II and phase III trials assessing novel HER2-targeted agents as third-line therapy or beyond for HER2-positive advanced breast cancer using search terms ‘breast cancer’ AND ‘HER2’ AND ‘advanced’ AND (‘phase II’ OR ‘phase III’).Results:Eight clinical trials reporting efficacy outcomes on third-line or greater HER2-directed therapy for HER2-positive advanced breast cancer were identified. In phase III trials, margetuximab and neratinib combinations demonstrated significant 1.3-month (hazard ratio, HR = 0.71, p < 0.001) and 0.1-month (HR = 0.76, p = 0.006) net improvements in median progression-free survival (PFS), respectively, with no significant improvements in overall survival (OS). Tucatinib added to trastuzumab and capecitabine demonstrated a significant 2.7-month improvement in median PFS (HR = 0.57, p < 0.00001) and a 5.5-month improvement in median OS (HR = 0.73, p = 0.004) in a randomized phase II trial, including significant clinical benefit for patients with brain metastases. Finally, trastuzumab-deruxtecan, zenocutuzumab, and poziotinib demonstrated benefit in phase II trials with the most robust overall response rate (62.0%) and median duration of response (18.2 months) observed for trastuzumab-deruxtecan among heavily pretreated patients.Conclusion:Tucatinib plus trastuzumab and capecitabine significantly prolongs OS, and promising preliminary response outcomes for trastuzumab-deruxtecan suggest that sequencing of these regimens following second-line therapy is reasonable.

【 授权许可】

CC BY-NC   
© The Author(s), 2022

【 图 表 】

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