S4046 A Rare Case of Palbociclib-Induced Pancolitis: Clinical Insights and Literature Review

Introduction: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard for HR+, HER2-negative advanced breast cancer. While generally well-tolerated, their adverse event profiles differ. Palbociclib is primarily linked to hematologic toxicity, with severe gastrointestinal toxicities like colitis being rare and underrecognized. Colitis presents a diagnostic challenge due to symptom overlap with infectious and inflammatory bowel diseases. Case Description/Methods: A 65-year-old woman with metastatic HR+ breast cancer on palbociclib, fulvestrant, and denosumab for 5 months developed a 2-week history of severe watery diarrhea and abdominal cramping. Infectious work up, including Clostridioides difficile and cytomegalovirus (CMV) polymerase chain reaction (PCR), were negative. Colonoscopy revealed moderate pancolitis. Palbociclib was held, and intravenous methylprednisolone was initiated for suspected drug-induced colitis, leading to rapid symptom improvement. Although colonic biopsies later showed CMV positivity, antiviral therapy was deferred given the negative CMV PCR and complete clinical resolution. Palbociclib was permanently discontinued. Discussion: This case highlights a rare but clinically significant adverse effect of palbociclib: drug-induced pancolitis. While GI side effects such as diarrhea are more commonly associated with abemaciclib, severe colitis with palbociclib has been reported in fewer than 5 cases in the literature. The clinical presentation often mimics inflammatory bowel disease or infectious colitis, making diagnosis challenging. In this case, negative infectious workup, endoscopic evidence of colitis, and rapid improvement following corticosteroids and drug cessation supported a drug-induced etiology. CMV positivity on biopsy was likely incidental, and the absence of viremia helped avoid unnecessary antiviral therapy. This case underscores the importance of clinician vigilance for rare toxicities, prompt withdrawal of the offending agent, and judicious use of immunosuppressive therapy. Early recognition and multidisciplinary management are key to optimizing outcomes.