WASHINGTON -- The FDA issued a warning Friday that CDK4/6 inhibitors for advanced breast cancer may cause rare but severe lung inflammation, and said fatalities had been reported.
Package warnings have been added to the three approved agents in the class -- palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) -- and breast cancer patients taking these agents should be monitored for pulmonary symptoms indicative of either pneumonitis or interstitial lung disease (ILD).
"The overall benefit of CDK4/6 inhibitors is still greater than the risks when used as prescribed," the agency said in the statement announcing the move. But clinicians should suspend treatment in patients "who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe ILD and/or pneumonitis."
Data from completed and ongoing postmarketing trials involving CDK4/6 inhibitors were reviewed and revealed the connection, the FDA said, but factors to identify at-risk patients have not been found.
Signs and symptoms of ILD and pneumonitis can include "hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded."
CDK4/6 inhibitors are used in combination with hormone therapies for patients with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The first of these agents, palbociclib, received FDA approval for women in 2015. This was followed by the 2017 approvals of ribociclib and abemaciclib. Most recently, palbociclib's indication was expanded to include men.