Moving forward from spleen response as an endpoint in randomized controlled trials in myelofibrosis

Abstract

Anticancer drugs should make patients live longer and/or feel better. Ideally, endpoints of cancer randomized controlled trials (RCTs) should demonstrate that a drug leads to an increase in overall survival (OS) and/or improvement in quality of life (QOL). With the aim of including smaller patient numbers, running shorter trials and thus getting new drugs to patients faster, cancer RCTs increasingly use (putative) surrogate endpoints. However, changes in surrogate endpoints often do not reliably predict improvements in OS and/or QOL. Furthermore, especially in later lines of cancer treatments or in cancer with a short life expectancy, use of surrogates does hardly speed up the availability of novel therapies but increases the advent of costly toxic drugs with uncertain benefit, thereby harming both patients and society. In myelofibrosis (MF) spleen response has extensively been used as a surrogate for clinical outcome. In this review we argue that there is no convincing evidence for the use of spleen response or other surrogate endpoints in MF, and that the use of surrogate endpoints in MF RCTs should be avoided altogether.