Antibody-drug conjugates in patients with advanced/metastatic HER2-low-expressing breast cancer: a systematic review and meta-analysis

Isabella Michelon; Maria Inez Dacoregio; Maysa Vilbert; Jonathan Priantti; Caio Ernesto do Rego Castro; Lucas Vian; Paolo Tarantino; Evandro de Azambuja; Ludimila Cavalcante

doi:10.1177/17588359241297079

Antibody-drug conjugates in patients with advanced/metastatic HER2-low-expressing breast cancer: a systematic review and meta-analysis

Ther Adv Med Oncol. 2024 Nov 20:16:17588359241297079. doi: 10.1177/17588359241297079. eCollection 2024.

Authors

Affiliations

¹ Department of Medicine, Catholic University of Pelotas, 373 Gonçalves Chaves, Pelotas 96010-000, Brazil.
² Department of Medicine, University of Centro Oeste, Guarapuava, Brazil.
³ Massachusetts General Hospital Cancer Center, Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁴ School of Medicine, Federal University of Amazonas, Manaus, Amazonas, Brazil.
⁵ Department of Medicine, University of Brasilia, Brasilia, Brazil.
⁶ Rede AMO de Campo Grande, Divisão de Oncologia, Departamento do Hospital CASSEMS de Campo Grande, Campo Grande, Mato Grosso do Sul, Brazil.
⁷ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
⁹ Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
¹¹ Institut Jules Bordet, Hopital Universitaire de Bruxelles and l'Université Libre de Bruxelles, Brussels, Belgium.
¹² Department of Medical Oncology and Hematology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA, USA.

Abstract

Background: Until recently, targeted therapies have failed to benefit patients with human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC). Nevertheless, antibody-drug conjugates (ADCs) have reshaped their prognosis.

Objectives: We performed a systematic review and meta-analysis to assess the effectiveness of ADCs in patients with HER2-low advanced/metastatic (a/m) BC.

Design: This study is a systematic review and meta-analysis.

Data sources: We searched PubMed, Embase, and Cochrane databases as well as the American Society of Clinical Oncology, European Society for Medical Oncology, and San Antonio Breast Cancer Symposium conference proceedings.

Methods: Studies evaluating ADCs (trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), MRG002, and RC48-ADC) in patients with HER2-low a/mBC were included. We used R software (v.4.2.2) and random effects models for all analyses. Heterogeneity was assessed using the I ² test.

Results: Overall, 14 studies were included (five real-world studies and nine clinical trials (CTs)), with 2883 HER2-low a/mBC patients: 808 received treatment of physician's choice (TPC), and 2075 ADCs. Most were treated with T-DXd (n = 1691), followed by SG (n = 310), MRG002 (n = 56), and RC48-ADC (n = 18). Patients treated with T-DXd achieved a significantly higher objective response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) than those receiving other ADCs. In the pooled analysis of four randomized CTs, ADCs statistically prolonged progression-free survival (n = 1828, hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.36-0.68, I ² = 82%, p < 0.001) and overall survival (n = 1546, HR 0.70, 95% CI 0.57-0.86, I ² = 43%, p < 0.001) compared with TPC. Patients on ADCs also achieved a greater antitumor response than TPC, including better ORR (odds ratio (OR), 3.7, 95% CI 2.5-5.6, I ² = 59%, p < 0.001), DCR (OR, 2.7, 95% CI 2.1-3.5, I ² = 0%, p < 0.001), and CBR (OR, 3.6, 95% CI 2.6-5.2, I ² = 56%, p < 0.01).

Conclusion: Our systematic review and meta-analysis confirms the efficacy of ADCs in HER2-low a/m BC patients over TPC. Future studies should focus on bringing ADCs into earlier lines of therapy in this population.

Trial registration: This study was registered in PROSPERO (CRD42024452962).

Keywords: HER2-low; MRG002; RC48-ADC; antibody–drug conjugates; breast cancer; human epidermal growth factor receptor 2; sacituzumab govitecan; trastuzumab deruxtecan.