Immune-checkpoint inhibitors and candidate surrogate endpoints for overall survival across tumour types: A systematic literature review.

Background: Surrogate endpoints (SEs) for overall survival (OS) are specific to therapeutic class. The objective of this review was to document all alternative endpoints studied for their association with OS in Immune-Checkpoint Inhibitors (ICI)-treated patients.

Methods: We searched PubMed and Embase for publications reporting the association between a clinical endpoint and OS in ICI-treated populations from 01/01/2003 to 03/31/2018.

Results: Out of 6,335 references identified, 24 were selected. Only 3 studies assessed surrogacy at both the patient and trial levels. The main traditional alternative endpoints included progression-free survival (N = 10) and objective response rate (N = 8). New alternative endpoints, such as durable response rate (N = 1) and intermediate response endpoint (N = 1) statistically better correlate with OS in the cancer types analysed.

Conclusion: Based on the published evidence, there is insufficient data to support validated SE for OS. Adequate surrogacy assessment of promising composite endpoints which consider a duration component is encouraged.