Quality of life of therapies for hormone receptor positive advanced/metastatic breast cancer (HR+/HER2- mBC): regulatory aspects and clinical impact in Europe

Background: In recent years the number of trials that incorporated health related quality of life (HRQoL) data has increased. The impact of HRQoL on the regulatory decision making in the European regulatory context and on clinical practice is not well established. We conduct an analysis of the role of QoL data extracted from the pivotal trials of the drugs approved for HR+/HER2- mBC, to discuss their impact on the regulatory decision making in the European regulatory context and the possible impact on clinical practice. Methods: We identified all products approved for mBC by the European Medicines Agency (EMA) based on the European public assessment reports (EPARs) that are publicly available on the agency’s website.The following substances has been evaluated: letrozole, anastrozole, exemestane, fulvestrant, ribociclib, palbociclib, abemaciclib, alpelisib. The results of the HRQoL analysis form the pivotal trials have been collected and a metanalysis has been performed to evaluate the impact of experimental drugs if compared to the standard treatments. All the EPARs available from the EMA website have been checked to verify the presence of the HRQoL in the discussion and in the benefit risk assessment. The related summary of medicine products characteristics (SmPCs) have been verified to evaluate the presence of the HRQoL data in the section 5.1 Results: 7 out of the 9 active substances taken in account in the current analysis incorporated the HRQoL data in the description of the result of the pivotal trials. Seventeen trial has been identified, in fourteen the QoL was included as a secondary endpoint. A global improvement in the global QoL, considering the Time To deterioration >10, was observed, pointing out the consistency of the efficacy of the new substances if compared to the standard treatment. As regards the approval process from the analysis of the EMA documents, the HRQoL were reported quite shortly and contained and discussed in the EPARs of eleven trials in the approval process and cited in three cases in the EPARs and summary of medicine products characteristics (SmPC). Conclusions: An effort should be done from all the stakeholders to increase the visibility of the HRQoL results in order to allow an increasing consideration in the approval process to make QoL data more easily and visibly available for the clinician and the patients. The evaluation should be reflected in the SmPC in order to increase the amount of information provided to the physician.