Palbociclib-Induced Apoptotic Colopathy: A Case Report and Review of the Literature

Cyclin-dependent kinase (CDK) 4/6 inhibitors (ribociclib, abemaciclib, and palbociclib) are standard first-line therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. While diarrhoea is a known adverse effect, severe gastrointestinal toxicity, particularly colitis, is rare and its histopathologic features are not well-characterized.

We report the case of a 65-year-old woman with HR-positive, HER2-negative metastatic breast cancer who developed severe diarrhoea and significant weight loss during palbociclib treatment. Her prior treatment included adjuvant chemotherapy, radiotherapy, and letrozole, followed by first-line treatment for metastatic disease with fulvestrant and abemaciclib. Due to recurrent grade II diarrhoea on abemaciclib, she was switched to palbociclib. One year after initiating palbociclib, she presented with 6-10 daily bowel movements, 11 kg weight loss, anaemia, and hypoalbuminemia. Infectious aetiologies were excluded. Imaging revealed pancolitis, and a colonoscopy showed multiple deep ulcers. A rectal biopsy demonstrated chronic proctitis with increased epithelial apoptosis. Palbociclib was discontinued, and oral budesonide was initiated, which led to clinical and endoscopic remission. She remained asymptomatic on fulvestrant monotherapy for over 6 months.

This rare case describes palbociclib-induced colitis with characteristic histopathologic findings of increased epithelial apoptosis, consistent with drug-induced apoptotic colopathy. To our knowledge, this is the first report of palbociclib-associated colitis with histological confirmation of apoptotic changes and successful treatment with budesonide. Clinicians should consider CDK4/6 inhibitors as a potential cause of severe gastrointestinal symptoms and recommend biopsy when the diagnosis is uncertain.

Although diarrhoea is a common side effect, palbociclib can, in rare cases, cause severe colitis with deep ulcers at video colonoscopy; internists should be aware of this underrecognized adverse effect.Histologic findings of increased epithelial apoptosis can support the diagnosis of drug-induced apoptotic colopathy.Oral budesonide, commonly used in microscopic colitis, may be an effective treatment for CDK4/6 inhibitor-induced colitis, offering a well-tolerated therapeutic option.