Immuno-oncology therapies (IOs) have revolutionised metastatic cancer management over the last decade. These are now being investigated in earlier stages of cancer, where surrogate survival endpoints such as relapse-free survival (RFS), disease-free survival (DFS), and pathological complete response (pCR) are needed to bridge the evidence gap prior to maturation of overall survival (OS) data. This research assesses surrogate survival endpoints in supporting access/reimbursement in early-stage cancers.

Publicly accessible assessments of early-stage cancer therapies by seven HTA-bodies (HAS, G-BA, Medicinrådet, NICE, SMC, PBAC, CADTH) up to May 2021 were extracted.

52 assessments of 11 drug:indication pairings were identified, which utilised four surrogate primary endpoints (RFS, DFS, invasive DFS, pCR). 30 were fully reimbursed, 11 restricted reimbursement, 11 not reimbursed. Payer support was defined as being considered clinically/patient-relevant and/or a valid surrogate to OS. RFS was the best-supported surrogate endpoint by HTA bodies (7/7), followed by DFS (5/7) and IDFS (5/7), while pCR (2/7) was least well-supported. NICE and SMC were the most supporting of access using surrogate endpoints, followed by G-BA, while CADTH was least supporting. Assessments were most positive where the magnitude of the surrogate benefit were greater/showed a superior benefit-risk and where early data showed a likely long-term OS benefit. However, some assessments from NICE/G-BA were conditional and contingent on more mature follow-up data being provided, and PBAC imposed a flow-on restriction limiting retreatment with IOs as later line(s) of therapy.

Several IOs already approved and reimbursed in the metastatic setting are being investigated in the early-stage setting using surrogate survival endpoints. These surrogate endpoints have been widely utilised for regulatory approval, and as shown here, HTA bodies are supportive of some surrogate endpoints based on their patient relevance and/or their validated OS correlation.