Surrogate endpoints for HTA decisions of breast cancer drugs: utility and pitfalls

Health technology assessment (HTA) of cancer drugs is important to identify whether drugs should be publicly funded. With increasing use of surrogate end points in clinical trials including breast cancer, a review of literature was done to synthesize evidence for validation of these surrogate end points and their potential role in HTA decisions pertaining to breast cancer.

Disease free survival (DFS) in human epidermal receptor 2 (HER2) positive early breast cancer remains the only validated surrogate end point. Other surrogate end points like pathological complete response (pCR) and event free survival (EFS) in early breast cancer (EBC) and objective response rate (ORR) and progression free survival (PFS) in advanced disease have not been validated for overall survival (OS). Moreover, surrogate end points for quality of life (QOL) have not been established and drugs that improve PFS can have detrimental effect on QOL. End points like pCR have excellent prognostic utility in individual patients but have weak correlation with survival at trial level.

Most surrogate end points used in breast cancer do not predict OS or QOL which makes it challenging to use them for decisions regarding public funding of cancer drugs. These findings are relevant to HTA agencies prior to making drug reimbursement decisions.