OBJECTIVES: To assess whether post-launch published evidence for HER2-positive early breast cancer (eBC) medicines could address the concerns identified by health technology assessment bodies (HTABs).

METHODS: Analysis of health technology assessment (HTA) reports of selected HER2-positive eBC medicines (trastuzumab, trastuzumab emtansine, neratinib, and pertuzumab) was conducted across national HTABs in France, Germany, Italy, Spain and England to identify evidence concerns at time of assessment. A targeted literature review (TLR) was conducted to identify evidence published post-HTA submission which could address the concerns.

RESULTS: 22 HTA decisions were found, containing the following evidence concerns: trial design, clinical outcomes, data maturity, safety and health-related quality of life (HRQoL). HTABs mainly questioned the use of event free survival (EFS) and pathological complete response (pCR) as surrogates for survival, the maturity of overall survival (OS) data and the inconsistent response rates based on hormone receptor (HR) status. The TLR identified several studies showing statistically significant correlation between pCR and EFS and a modelling study supporting the use of pCR as a predictor of OS. Evidence suggests that HR status impacts survival outcomes in patients with HER2+ eBC.

CONCLUSION: Patients achieving pCR have significantly improved EFS. Given long-term survival of eBC patients, OS remains immature. However, mature maintenance of EFS indicates OS benefit could be established with further readouts. More research is required around HR status being predictive or prognostic in HER2 eBC. Overall, pCR and EFS can be relevant endpoints for HTABs in reliably assessing patient benefit and making HTA decisions, and HTABs concerns can be addressed with subsequent evidence.