OBJECTIVES

Cyclin dependent kinase (CDK) 4/6 inhibitors are a newer class of oral medications used in the treatment of breast cancer, of which there are three currently approved: palbociclib, ribociclib, and abemaciclib. In September 2019, the U.S. Food and Drug Administration (FDA) added a warning to the package insert for all three CDK 4/6 inhibitors highlighting the risk of interstitial lung disease (ISLD) and pneumonitis. We aimed to assess the potential risk of lung injury for CDK4/6 inhibitors in a real-world population.

METHODS

: A disproportionality analysis was conducted of the U.S. FDA’s Adverse Event Reporting System (FAERS) using the AERSMine platform. We analyzed adverse reactions for palbociclib, ribociclib, and abemaciclib from the quarter following their FDA approval through September 2019. We calculated reporting odds ratios (ROR), proportional reporting ratios (PRR), and corresponding 95% confidence intervals (CI) for the reactions of ILSD, pneumonitis, and a composite of the two events.

RESULTS

: While only abemaciclib had a significantly increased risk of ISLD (abemaciclib ROR: 11.13, 95% CI: 8.58-14.43; ribociclib ROR: 0.95, 95% CI: 0.53-1.72; palbociclib ROR: 1.02, 95% CI: 0.83-1.24), all CDK 4/6 inhibitors had a significant signal for pneumonitis (abemaciclib ROR: 2.30, 95% CI: 1.09-4.83; ribociclib ROR: 3.59, 95% CI: 2.38-5.41; palbociclib ROR: 1.94, 95% CI: 1.60-2.35). In addition, all CDK 4/6 inhibitors had a significant signal on the composite outcome. Abemaciclib had an 800% increased risk (ROR: 8.00, 95% CI: 6.25-10.22) of the composite outcome compared to all other medications, whereas ribociclib had an 90% increased risk (ROR: 1.90, 95% CI: 1.35-2.66) and palbociclib had a 35% increased risk (ROR: 1.35, 95% CI: 1.18-1.55).

CONCLUSIONS

: All CDK 4/6 inhibitors had an increased risk of pneumonitis as well as the composite of either ISLD or pneumonitis. Future studies are needed to assess the association and causality of the CDK 4/6 inhibitor class on lung inflammation.