Assessment of Food and Drug Administration– and European Medicines Agency–Approved Systemic Oncology Therapies and Clinically Meaningful Improvements in Quality of Life

Abstract

For patients with cancer treated with palliative intent, quality of life (QOL) is a critical aspect of treatment decision-making, alongside survival. However, regulatory approval can be based solely on survival measures or antitumor activities, without QOL evidence. To investigate whether recently approved oncology therapies demonstrate clinically meaningful improvements in QOL. This systematic review study identified oncology drug indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) from January 2006 to December 2017 and supporting clinical trials (QOL publications identified to October 2019). Indications were evaluated for the presence of published QOL evidence; QOL benefits according to the American Society of Clinical Oncology Value Framework version 2.0 (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) QOL bonus criteria; and clinically meaningful improvements in QOL beyond minimal clinically important differences. Hematology trials were not evaluated by ESMO-MCBS. Associations between QOL evidence and approval year were examined using logistic regression models. In total, 214 FDA-approved (77 [36%] hematological) and 170 EMA-approved (52 [31%] hematological) indications were included. QOL evidence was published for 40% and 58% of FDA- and EMA-approved indications, respectively. QOL bonus criterion for ASCO-VF and ESMO-MCBS was met in 13% and 17% of FDA-approved and 21% and 24% of EMA-approved indications, respectively. Clinically meaningful improvements in QOL beyond minimal clinically important differences were noted in 6% and 11% of FDA- and EMA-approved indications, respectively. Availability of published QOL evidence at the time of approval increased over time for EMA (odds ratio [OR], 1.13; P = .03), however not for FDA (OR, 1.10; P = .12). Over time, no increase in awarded QOL bonuses or clinically meaningful improvements in QOL were found. The findings of this systematic review suggest that approved systemic oncology therapies often do not have published evidence to suggest QOL improvement, despite its recognized importance. Of indications with evidence of statistical improvement, few have demonstrated clinically meaningful improvements.