cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung disease and pneumonitis

Last edited 09/2021 and last reviewed 07/2023

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung disease and pneumonitis

CDK4/6 inhibitors

• are authorised for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant
• in premenopausal or perimenopausal women, the endocrine therapy should be combined with a luteinising-hormone-releasing hormone (LHRH) agonist
• cases of interstitial lung disease and pneumonitis have been reported with the use of CDK4/6 inhibitors (abemaciclib , palbociclib , ribociclib)
  • abemaciclib, the product information notes that 3.4% of participants treated in clinical trials (n=768) had interstitial lung disease or pneumonitis of any grades of severity
  • palbociclib, the product information notes that 1.4% of participants treated in clinical trials (n=872) had interstitial lung disease or pneumonitis of any grade
  • ribociclib, the product information notes that interstitial lung disease (any grade 0.3%, including 0.1% grade 3) was reported in the ribociclib-treated group in clinical studies, with no cases in the placebo-treated group. Pneumonitis was reported in both the ribociclib and the placebo-treated groups (any grade 0.4%; with no grade 3 or 4 events in either group)

• abemaciclib , palbociclib and ribociclib are indicated for some locally advanced or metastatic breast cancer (see product information for full indications)
• there have been reports of interstitial lung disease and pneumonitis with these medicines, in some cases severe or fatal
• during clinic appointments, ask patients about pulmonary symptoms indicative of interstitial lung disease and pneumonitis, such as cough or dyspnoea, and advise them to seek advice right away if they occur
• evaluate patients with new or worsening respiratory symptoms, refer to the Summary of Product Characteristics (SmPC; linked above), particularly advice in sections 4.2 and 4.4, and consider dose interruption, modification, or discontinuation according to the severity of the event
• ensure patients are provided with a copy of the Patient Information Leaflet (PIL), which provides information about the medicine and explains the symptoms that patients should be aware of
• report all suspected adverse drug reactions associated with CDK4/6 inhibitors to the Yellow Card scheme

Reference:

• Drug Safety Update volume 14, issue 11: June 2021: 1.