Life expectancy of patients with non-metastatic prostate cancer may exceed 10 years, making overall survival an impractical primary efficacy endpoint. Therefore, pivotal trials in non-metastatic castration-resistant prostate cancer (M0 CRPC) have proposed metastasis-free survival (MFS) as an intermediate primary efficacy endpoint. While new oncology drugs may be conditionally approved by regulators based on attaining intermediate efficacy endpoints, their acceptance by payers varies widely across regions and agencies. This research aimed to assess the acceptance of MFS by payers to demonstrate clinical benefit to patients.
A targeted search for products with MFS as an endpoint was performed. Health technology assessments (HTAs) of these products and analogues in early-stage oncology indications published from January 2011–March 2016 were obtained from HTA agencies around the globe (NICE, SMC, G-BA, IQWiG, HAS, PBAC and TLV).
MFS was used as the primary endpoint for six products, five in M0 CRPC and one in melanoma stage III; however, all are yet to receive regulatory approval. In a search of analogue indications, 40 HTAs of seven products in 10 different indications were found. Notably, progression-free survival (PFS) was the primary endpoint in most (9/10) indications and its definitions closely resembled MFS in M0 CRPC. No assessments included demonstrated statistically significant survival benefits and all submissions relied on intermediate primary endpoints to demonstrate clinical benefits (36 PFS; four objective response rate). A correlation between PFS gain of ≥5 months and positive recommendations was observed for most agencies, except in Germany (IQWiG and G-BA) and France (HAS), where the acceptance of intermediate endpoints remains challenging.
Payers’ acceptance of intermediate endpoints has increased over time and is mainly driven by the effect size of the demonstrated benefit. However, benefit ratings in France remain low and strict endpoint validation guidelines seem to hinder acceptance in Germany.