Presentation (CTI)

OBJECTIVES: Antibody-drug conjugates (ADCs) have expanded treatment options in breast cancer (BC), particularly across HER2-positive, HER2-low, and triple-negative subtypes. Supporting trials frequently rely on surrogate endpoints such as progression-free survival (PFS), disease-free survival (DFS), and pathological complete response (pCR), often with immature overall survival (OS) data at evaluation. This study assessed surrogate endpoint use in HTA submissions and resulting outcomes across theEU4 (Germany, France, Italy and Spain) and the UK.
METHODS: Review of HTA reports for ADCs in BC was conducted across the EU4 and UK HTA websites and the INAHTA database. Extracted data included indication, trial design, comparator, and primary endpoint, enabling cross-country comparisons.
RESULTS: A total of 49 HTA documents were identified, with none for Italy or Spain. Seven submissions (14%) were in early breast cancer and 42 (86%) in metastatic/advanced. Of these, 35 were included (14 UK ongoing/pending appraisals excluded). ADCs assessed included trastuzumab deruxtecan, sacituzumab govitecan, trastuzumab emtansine, and datopotamab deruxtecan. PFS was the most common (93%) primary endpoint, with OS frequently immature at submission. Overall, 66% of assessments received positive recommendations, 13% conditional/restricted, and 20% negative or "benefit not proven." French assessments were generally more accepting of surrogate endpoint evidence when supported by overall clinical benefit (90% positive), while Germany and UK more frequently highlighted uncertainty related to immature survival data (50% and 63% positive, respectively).
CONCLUSIONS: Surrogate endpoints are widely used in clinical evidence for ADCs in breast cancer. The predominance of metastatic submissions aligns with reliance on PFS and a higher likelihood of positive recommendations despite immature OS data. Findings suggest broad HTA acceptance in high unmet need settings, although cross-country differences indicate that surrogate evidence interpretation remains context dependent. The absence of identified reports from Italy and Spain likely reflects methodological and accessibility limitations rather than absence of HTA activity, warranting further investigation.