Efficacy and Safety of Antibody-Drug Conjugates (ADCs) in Pretreated Breast Cancer: A Systematic Literature Review (SLR)
Author(s)
Patricia Dorling, MS, PharmD, PhD1, Aanchal Goswami, MPH2, Prateek Das, MPH2, Bhawna Mangla, MPH2, sachin kumar, MPH2, Vaibhav Sharma, MPH2, Amin Haiderali, MBA, MPH3, Tanya Keenan, MS, PharmD, PhD3.
1Merck & Co Inc., Rahway, NJ, USA, 2CHEORS LLC, Chalfont, PA, USA, 3Merck & Co Inc., North Wales, PA, USA.
1Merck & Co Inc., Rahway, NJ, USA, 2CHEORS LLC, Chalfont, PA, USA, 3Merck & Co Inc., North Wales, PA, USA.
OBJECTIVES: ADCs are an emerging class of targeted therapies in breast cancer. This SLR assessed ADC safety and efficacy in non-TNBC breast cancer patients previously treated with surgery or systemic therapies, irrespective of the treatment line.
METHODS: Following Cochrane guidelines, we searched MEDLINE, Embase, and Cochrane databases for the last 10 years, along with clinical trial registries and relevant conferences.
RESULTS: 30 clinical trials (27 in locally advanced and/or metastatic (LA/m), three in early-stage) were identified, evaluating five ADCs across various subtypes (HR+/-HER2+, HR+/HER2- and HER2+ with unreported HR status). In LA/m,17 trials were for Trastuzumab emtansine (T-DM1), five for Sacituzumab govitecan (SG), three for Trastuzumab deruxtecan (T-Dxd), and one each for Datopotamab deruxtecan (Dato-Dxd), and Enfortumab vedotin (EV). T-DM1 showed median progression-free survival (mPFS) of 4.1-16.9 (HR+/-HER2+) months; median overall survival (mOS) of 9.5(HR+/HER2-) to 35.1(HR+/-HER2+) months. Grade≥3 treatment-related adverse events (TRAEs) were reported in 20.0% (HER2+ with unreported HR status) to 56.0%(HR+/-HER2+) patients and AE-related discontinuation rates (AEDR) of 0-28%. SG reported mPFS of 4.4-8.4 months, mOS 12.0-17.1 months; grade≥3 AEs 74.0-82.0% patients and AEDR of 0-6%. T-Dxd showed mPFS of 16.7 (HR+/-HER2+) to 21.0 (HER2+ with unreported HR status) months, and mOS 29.1-35.7 (HR+/-HER2+) months. Grade ≥3 TRAEs occurred in 41.0-53.8% (HR+/-HER2+) patients with TRAE discontinuations 14%- 17.9% (HR+/-HER2+). Dato-Dxd demonstrated mPFS 6.9 (HR+/HER2-) months; grade ≥3 TRAEs rate 20.8% (HR+/HER2-); TRAE discontinuation rate of 2.5% (HR+/HER2-). EV treatment showed mPFS of 5.4 (HR+/HER2-) months, mOS 19.8 (HR+/HER2-) months; safety data not reported. In early-stage disease, T-DM1 (2 trials) reported SAEs in 12.7%-21.4% patients and AEDR of 17.9%; SG (1 trial) reported AEDR in 13.6% patients. Data for SAEs, mPFS and mOS were not reported.
CONCLUSIONS: ADCs demonstrated clinically meaningful benefit across pretreated breast cancer subtypes with acceptable risk-benefit profile.
METHODS: Following Cochrane guidelines, we searched MEDLINE, Embase, and Cochrane databases for the last 10 years, along with clinical trial registries and relevant conferences.
RESULTS: 30 clinical trials (27 in locally advanced and/or metastatic (LA/m), three in early-stage) were identified, evaluating five ADCs across various subtypes (HR+/-HER2+, HR+/HER2- and HER2+ with unreported HR status). In LA/m,17 trials were for Trastuzumab emtansine (T-DM1), five for Sacituzumab govitecan (SG), three for Trastuzumab deruxtecan (T-Dxd), and one each for Datopotamab deruxtecan (Dato-Dxd), and Enfortumab vedotin (EV). T-DM1 showed median progression-free survival (mPFS) of 4.1-16.9 (HR+/-HER2+) months; median overall survival (mOS) of 9.5(HR+/HER2-) to 35.1(HR+/-HER2+) months. Grade≥3 treatment-related adverse events (TRAEs) were reported in 20.0% (HER2+ with unreported HR status) to 56.0%(HR+/-HER2+) patients and AE-related discontinuation rates (AEDR) of 0-28%. SG reported mPFS of 4.4-8.4 months, mOS 12.0-17.1 months; grade≥3 AEs 74.0-82.0% patients and AEDR of 0-6%. T-Dxd showed mPFS of 16.7 (HR+/-HER2+) to 21.0 (HER2+ with unreported HR status) months, and mOS 29.1-35.7 (HR+/-HER2+) months. Grade ≥3 TRAEs occurred in 41.0-53.8% (HR+/-HER2+) patients with TRAE discontinuations 14%- 17.9% (HR+/-HER2+). Dato-Dxd demonstrated mPFS 6.9 (HR+/HER2-) months; grade ≥3 TRAEs rate 20.8% (HR+/HER2-); TRAE discontinuation rate of 2.5% (HR+/HER2-). EV treatment showed mPFS of 5.4 (HR+/HER2-) months, mOS 19.8 (HR+/HER2-) months; safety data not reported. In early-stage disease, T-DM1 (2 trials) reported SAEs in 12.7%-21.4% patients and AEDR of 17.9%; SG (1 trial) reported AEDR in 13.6% patients. Data for SAEs, mPFS and mOS were not reported.
CONCLUSIONS: ADCs demonstrated clinically meaningful benefit across pretreated breast cancer subtypes with acceptable risk-benefit profile.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO89
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Oncology