Cardiac safety of afatinib: a review of data from clinical trials

Area of Science:

• Oncology
• Cardiology
• Pharmacology

Background:

• Afatinib is an irreversible ErbB family blocker targeting EGFR, HER2, and HER4.
• It is approved for advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations.
• Concerns exist regarding cardiac dysfunction with anti-HER2 therapies, necessitating cardiac safety evaluation of afatinib.

Purpose of the Study:

• To report cardiac safety data for afatinib in NSCLC patients.
• To evaluate the incidence of cardiac failure adverse events (CF-AEs) and left ventricular ejection fraction (LVEF) reductions.
• To assess afatinib's cardiac safety profile in comparison to chemotherapy and placebo.

Main Methods:

• Cardiac data were analyzed from Phase III trials LUX-Lung 3 (LL3) and LUX-Lung 1 (LL1).
• CF-AEs, including symptomatic cardiac failure and depressed LVEF, were assessed in afatinib-treated patients versus chemotherapy or placebo.
• Pooled data from 49 trials involving 3865 afatinib-treated patients were also analyzed.

Main Results:

• Time at risk-adjusted CF-AE rates were similar for afatinib versus placebo in LL1 (2.40 vs 2.23) and versus chemotherapy in LL3 (2.28 vs 2.92).
• The pooled afatinib CF-AE rate was 2.88 events/100 patient-years.
• Clinically significant LVEF reductions were less frequent with afatinib compared to chemotherapy in LL3 (6.3% vs 13.3%) and similar to placebo in LL1 (4.6% vs 4.1%).

Conclusions:

• Afatinib was not associated with an increased risk of cardiac failure in the analyzed clinical trials.
• No significant association was found between afatinib treatment and reductions in left ventricular ejection fraction.
• The findings support the cardiac safety of afatinib in the treatment of NSCLC.