Cardiac Safety of Osimertinib: A Review of Data.

Purpose: Osimertinib is a third-generation, CNS-active, irreversible, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits both EGFR-TKI-sensitizing and T790M resistance mutations. We assess the cardiac failure risk in patients receiving osimertinib by evaluating the available data.

Methods: Post hoc analyses of cardiac data from (1) studies in patients with advanced non-small-cell lung cancer, FLAURA (osimertinib, n = 279; comparator EGFR-TKI, n = 277) and AURA3 (osimertinib, n = 279; chemotherapy, n = 140), and (2) a pooled data set of patients treated with osimertinib 80 mg from across the clinical trial program (n = 1,142), including cardiac failure-related adverse events and left ventricular ejection fraction (LVEF) reductions.

Potential Procedural Efficiencies and Challenges of Combining Multiple Type II Variations into a Single EU-RMP.

The process for amending a European Union Risk Management Plan (EU-RMP) with new information requires the submission of a formal variation procedure, of which there are four distinct categories: Type IA, Type IB, Type II, and 'Extension of a marketing authorisation' (or simply 'extension'). A Type II variation, in accordance with the above-referenced European Commission regulation, is defined as 'a variation that is not an extension of the marketing authorisation (line extension) and that may have a significant impact on the quality, safety or efficacy of a medicinal product'. Additional detail regarding which type of variation should be submitted in specific circumstances is provided in the accompanying guideline.