lung cancer

Cardiac safety of osimertinib: Review of data

Osimertinib is a very potent third-generation, CNS-active reversible oral EGFR targeting TKI, that selectively inhibits both EGFR sensitizing and T790M resistance mutations.  The authors wanted to assess the cardiac failure risk in patients receiving osimertinib through analysis of available data.

Post hoc analysis from the following clinical trials were performed, FLAURA and AURA3.  279 and 279 patients were reviewed respectively, who were treated with osimertinib.  Pooled data set of patients treated with osimertinib 80 mg from across the clinical trial program at 1,142 patients including cardiac failure related adverse events in left ventricular ejection fraction reductions.  Left ventricular ejection fraction pharmacokinetic and pharmacodynamic analysis of the pooled data set was performed.  The sponsors database was analyzed for cardiac failure related adverse events.  A literature search was also performed.

Decrease in left ventricular ejection fraction from a baseline of 10 or more percentage points to an absolute value of less than 50% following osimertinib treatment were observed in 8 and 14 patients in the FLAURA and AURA3 trials respectively.  It was seen in 35 patients in the pooled population.  Most events were asymptomatic and resolved without treatment of the event or osimertinib discontinuation.  The pharmacokinetic and pharmacodynamic analysis did not show a relationship between drug exposure and decreased ejection fraction from baseline.  No trend or pattern was suggested from literature review.

The authors concluded “these data do not suggest a causal relationship between osimertinib and cardiac failure.  However, because of LVEF decreases that were observed in patients with cardiac risk factors before osimertinib treatment, cardiac monitoring, including an assessment of LVEF at baseline and during osimertinib treatment, is advised”