Exploring Synergistic ADC-ICI Combinations in Breast Cancer: Clinical Insights From a Scoping Review
Author(s)
Padma Ramasamy, PhD1, Shaurya Deep Bajwa, MBA, MSc1, KAPIL KHAMBHOLJA, PhD2, Rital Patel, MSc2.
1Catalyst Clinical Research, Thiruvananthapuram, India, 2Catalyst Clinical Research, Baroda, India.
1Catalyst Clinical Research, Thiruvananthapuram, India, 2Catalyst Clinical Research, Baroda, India.
OBJECTIVES: Despite therapeutic advances, breast cancer remains a major cause of cancer-related mortality, particularly in aggressive subtypes, including triple-negative (TNBC) and HER2+ disease, associated with poor prognoses. Although antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) demonstrated clinical benefit, monotherapy resistance limits the durability of response. This study aims to explore the evolving clinical landscape of ADC-ICI combination therapies in breast cancer, with emphasis on efficacy, safety, and mechanistic rationale to inform translational research and regulatory decision-making.
METHODS: This review followed the JBI and PRISMA-ScR methodology. A systematic search was performed across PubMed, Google Scholar, and ClinicalTrials.gov for English-language studies published between March 2015 and March 2025. Eligible studies evaluated ADC-ICI combinations in breast cancer subtypes. Extracted date included study design, therapeutic agents, patient subgroups, and clinical endpoints, including overall response rate (ORR), progression-free survival (PFS), overall survival (OS), immune markers, and adverse events (AEs).
RESULTS: Eleven clinical studies involving approximately 498 breast cancer patients evaluated various ADC-ICI combinations. The pooled ORR was 56% (95CI: 46-70) and median OS ranged from 11.6 to 18.5 months. Subgroup analysis showed that in HER2⁺ metastatic breast cancer, Trastuzumab Deruxtecan (T-DXd) plus Nivolumab achieved an ORR of 65.6% with median PFS of up to 11.6 months. In TNBC, Sacituzumab govitecan plus Atezolizumab and Datopotamab deruxteca plus Durvalumab showed ORRs of 76.7% and 79.0%, respectively. Common adverse events included fatigue, gastrointestinal symptoms, and interstitial lung disease with T-DXd. The incidence of Grade ≥3 AEs ranged from 28% to over 40% across studies.
CONCLUSIONS: These findings highlight the clinical promise of ADC-ICI combinations, especially in TNBC and HER2⁺ subgroups. However, variability in outcomes and toxicity underscores the need for further research to refine treatment selection, validate predictive biomarkers, and evaluate long-term benefits to support clinical implementation and inform HTA and reimbursement frameworks.
METHODS: This review followed the JBI and PRISMA-ScR methodology. A systematic search was performed across PubMed, Google Scholar, and ClinicalTrials.gov for English-language studies published between March 2015 and March 2025. Eligible studies evaluated ADC-ICI combinations in breast cancer subtypes. Extracted date included study design, therapeutic agents, patient subgroups, and clinical endpoints, including overall response rate (ORR), progression-free survival (PFS), overall survival (OS), immune markers, and adverse events (AEs).
RESULTS: Eleven clinical studies involving approximately 498 breast cancer patients evaluated various ADC-ICI combinations. The pooled ORR was 56% (95CI: 46-70) and median OS ranged from 11.6 to 18.5 months. Subgroup analysis showed that in HER2⁺ metastatic breast cancer, Trastuzumab Deruxtecan (T-DXd) plus Nivolumab achieved an ORR of 65.6% with median PFS of up to 11.6 months. In TNBC, Sacituzumab govitecan plus Atezolizumab and Datopotamab deruxteca plus Durvalumab showed ORRs of 76.7% and 79.0%, respectively. Common adverse events included fatigue, gastrointestinal symptoms, and interstitial lung disease with T-DXd. The incidence of Grade ≥3 AEs ranged from 28% to over 40% across studies.
CONCLUSIONS: These findings highlight the clinical promise of ADC-ICI combinations, especially in TNBC and HER2⁺ subgroups. However, variability in outcomes and toxicity underscores the need for further research to refine treatment selection, validate predictive biomarkers, and evaluate long-term benefits to support clinical implementation and inform HTA and reimbursement frameworks.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO118
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Oncology