FDA and EMA approval of datopotamab-deruxtecan: A paradigm shift in breast cancer drug evaluation?

Abstract

The January 2025 FDA and EMA approvals of datopotamab-deruxtecan for metastatic HR-positive, HER2-negative breast cancer represents an unprecedented regulatory decision. The TROPION-Breast01 trial demonstrated significant progression-free survival improvement (6.9 vs 4.9 months; HR 0.63) but failed to show overall survival benefit (18.6 vs 18.3 months; HR 1.01)[1,2]. This marks the first full approval of a breast cancer therapeutic that failed a co-primary overall survival endpoint. Subsequently, the European Medicines Agency also granted marketing authorization in January 2025, creating a concerning precedent across both major regulatory agencies. With both major regulatory agencies now having approved this agent, breast cancer specialists must grapple with fundamental questions: What constitutes meaningful clinical benefit in heavily pretreated patients? How should we interpret trials with divergent endpoint results? This commentary examines the implications for breast cancer practice and argues for urgent reassessment of evidence standards as the therapeutic landscape evolves.