Journal: PLoS medicine
This article is a concise, practice-oriented review of the current and emerging role of antibody-drug conjugates (ADCs) in advanced breast cancer.
Key points:
- ADCs as a major treatment class: ADCs have become a major treatment class across all biological subtypes of advanced breast cancer, not just HER2-positive disease.
- Evidence gap in treatment sequencing: Their rapid clinical uptake has outpaced the evidence base for optimal sequencing—there is limited data on how best to position different ADCs relative to each other and to standard chemotherapy, endocrine therapy, and targeted agents.
- Unresolved trial design issues:
- Ethical concerns: Ethical questions arise when control arms may not reflect evolving standards of care.
- Types of trials needed: There is a need for trials that answer sequencing and combination questions rather than only single-agent efficacy.
- Generalizability challenges: Challenges exist in designing studies for molecularly selected subgroups while maintaining generalizability.
- Drug tolerability and safety:
- Distinct toxicity profiles: Distinct toxicity profiles (e.g., cytopenias, neuropathy, interstitial lung disease, ocular and GI toxicities) demand careful management.
- Long-term safety: Long-term safety and cumulative toxicity in chronically treated patients remain incompletely defined.
- Concerns about mono-national development programs:
- Limited generalizability: Restricting pivotal studies to single countries risks limited generalizability and may delay global access.
- Need for multinational programs: More inclusive, multinational programs are needed to ensure diverse representation and worldwide applicability of results.
Overall: The publication underscores that while ADCs are transforming advanced breast cancer management, the field urgently needs rational sequencing strategies, more sophisticated and ethical trial designs, better toxicity characterization and mitigation, and broader, globally relevant development pathways.