Safety and Efficacy of Antibody Drug Conjugate (ADCs) in Pretreated Locally Advanced/Metastatic (LA/m) Triple-Negative Breast Cancer (TNBC): Systematic Literature Review (SLR)
Author(s)
Patricia Dorling, MS, PharmD, PhD1, Shalini Bagga, PhD2, Vaneet Kaur Khurana, MPH3, Prashant Soni, PhD4, Alifiya Rounak, PhD5, Amin Haiderali, MBA, MPH6, Tanya Keenan, MD1.
1Merck & Co, Rahway, NJ, USA, 2CHEORS powered by BioBridges, North Wales, PA, USA, 3CHEORS, Cambridge, ON, Canada, 4CHEORS, Delhi, India, 5CHEORS, North Wales, PA, USA, 6Merck, North Wales, PA, USA.
1Merck & Co, Rahway, NJ, USA, 2CHEORS powered by BioBridges, North Wales, PA, USA, 3CHEORS, Cambridge, ON, Canada, 4CHEORS, Delhi, India, 5CHEORS, North Wales, PA, USA, 6Merck, North Wales, PA, USA.
OBJECTIVES: TNBC is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. ADCs offer a promising targeted approach. This SLR aims to summarize the evidence on safety and efficacy of ADCs in LA/m TNBC patients previously treated with systemic anticancer therapy.
METHODS: This SLR was conducted using Cochrane's methodology across MEDLINE, Embase, and Cochrane from Jan 2014 to Sept 2024. Data was supplemented with relevant trial registries and conference proceedings.
RESULTS: Seven trials were identified for LA/m TNBC patients previously treated with systemic anticancer therapy, with most of the trials evaluating patients with prior two lines of therapy: six for sacituzumab govitecan (SG), and one for enfortumab vedotin (EV). Four SG trials evaluated monotherapy (IMMU-132-01, PhI/II; ASCENT, PhIII; Bardia et al. 2018, PhII; EVER-132-001, PhII), and three were single-arm (mPFS ~5.5 months; mOS 12.7-14.7 months; Grade ≥3 AEs 79%; AE-related discontinuations 0-8%). One pivotal RCT (ASCENT) showed significant improvement of SG over chemotherapy (mPFS 4.8 vs 1.7 months; mOS 11.8 vs 6.9 months; 73% Grade ≥3 AEs; 5% discontinuations).Two SG single-arm combination studies (NCT04039230, PhII; NCT05113966, PII) reported mPFS of 6.2 months (SG+talazoparib) and 4.1 months (SG+trilaciclib), with mOS of 18.0 and 17.9 months, respectively. Serious AEs occurred in 38.5% (SG+talazoparib) and 20% (SG+trilaciclib), with one discontinuation reported due to AEs. However, no Grade ≥3 AEs were reported in the trials. Preliminary data from an ongoing EV trial showed mPFS of 3.5 months and mOS of 12.9 months; Grade ≥3 AEs and discontinuations due to AE were not assessed.
CONCLUSIONS: ADCs have demonstrated meaningful clinical benefits in pretreated LA/m TNBC, with varying safety profiles. Ongoing research into combination therapies and biomarker-driven patient selection is essential to optimize their integration into clinical practice.
METHODS: This SLR was conducted using Cochrane's methodology across MEDLINE, Embase, and Cochrane from Jan 2014 to Sept 2024. Data was supplemented with relevant trial registries and conference proceedings.
RESULTS: Seven trials were identified for LA/m TNBC patients previously treated with systemic anticancer therapy, with most of the trials evaluating patients with prior two lines of therapy: six for sacituzumab govitecan (SG), and one for enfortumab vedotin (EV). Four SG trials evaluated monotherapy (IMMU-132-01, PhI/II; ASCENT, PhIII; Bardia et al. 2018, PhII; EVER-132-001, PhII), and three were single-arm (mPFS ~5.5 months; mOS 12.7-14.7 months; Grade ≥3 AEs 79%; AE-related discontinuations 0-8%). One pivotal RCT (ASCENT) showed significant improvement of SG over chemotherapy (mPFS 4.8 vs 1.7 months; mOS 11.8 vs 6.9 months; 73% Grade ≥3 AEs; 5% discontinuations).Two SG single-arm combination studies (NCT04039230, PhII; NCT05113966, PII) reported mPFS of 6.2 months (SG+talazoparib) and 4.1 months (SG+trilaciclib), with mOS of 18.0 and 17.9 months, respectively. Serious AEs occurred in 38.5% (SG+talazoparib) and 20% (SG+trilaciclib), with one discontinuation reported due to AEs. However, no Grade ≥3 AEs were reported in the trials. Preliminary data from an ongoing EV trial showed mPFS of 3.5 months and mOS of 12.9 months; Grade ≥3 AEs and discontinuations due to AE were not assessed.
CONCLUSIONS: ADCs have demonstrated meaningful clinical benefits in pretreated LA/m TNBC, with varying safety profiles. Ongoing research into combination therapies and biomarker-driven patient selection is essential to optimize their integration into clinical practice.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO216
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Oncology