OBJECTIVES

Overall survival (OS) is a measure of efficacy for oncology therapies targeting metastatic disease. As science evolves, therapies are being developed to treat disease in the early-stage, non-metastatic setting where treatment intent is curative. Given the early setting, and prolonged survival, demonstrating OS within a clinical trial setting may not be feasible. In these cases, disease free survival (DFS) is a relevant regulatory endpoint. Our objective was to assess whether DFS was an acceptable endpoint for HTA decision-making purposes.

METHODS

We identified HTA decisions on solid tumour therapies where (invasive) DFS was used as a primary clinical trial endpoint across 7 HTA agencies up until Q1 2021. HTA reports were assessed to understand the role of DFS and other evidence in HTA outcomes.

RESULTS

Thirty-four HTA outcomes were identified covering four therapies (pertuzumab, trastuzumab, trastuzumab emtansine and neratinib), all in the HER2+ breast cancer (BC) setting. DFS hazard ratios (HR) ranged from 0.50 to 0.81, and despite differences identified in the definition of DFS across each trial, DFS was accepted as a relevant endpoint by all HTA agencies. Additionally, superiority against standard of care and a tolerable safety profile supported by patient reported outcome data led to more HTA recommendations or higher ratings.

CONCLUSIONS

This analysis shows that DFS is a clinically relevant endpoint for HTA purposes in the early-stage, non-metastatic treatment setting. Agencies were more likely to recommend treatments when the HR was more favorable and statistically significant, and patient quality of life was not adversely impacted. Although these results are based on data from HER2+ BC therapies, this analysis suggests that DFS is a clinically relevant endpoint for therapies being evaluated in HER2- BC and other solid tumours such as lung.