Switching CDK4/6 inhibitors to overcome toxicity in HR-positive/HER2-negative advanced breast cancer.

Background and aimThere is limited data on the safety of switching between CDK4/6i to address toxicity-related permanent discontinuation in patients with HR+/HER2- advanced breast cancer (ABC).To overcome this issue, this international observational study included consecutive HR+/HER2- ABC patients treated with CDK4/6i at two cancer centers, who switched the CDK4/6i for toxicity. The study aimed to evaluate the safety, feasibility, and clinical impact of this approach.ResultsAmong 1413 patients, 67 (4.5%) switched CDK4/6i due to toxicity. The median time to switch was three months. Adverse events leading to switch were mainly hematologic and hepatic. Recurrence of the same toxicity occurred in 30% of patients, but with lower severity for neutropenia (p=0.047) and hepatotoxicity (p=0.005). Notably, among the 67 patients who switched CDK4/6i, only seven (10%) ultimately required permanent discontinuation of the second CDK4/6i for toxicity, primarily for abemaciclib-induced diarrhea, suggesting that switching may represent a promising strategy to avoid treatment interruption. Median progression-free survival from the start of the first CDK4/6i was 16.8 monthsConclusionIn conclusion, switching CDK4/6i appears to be a safe and pragmatic strategy to address toxicity-related permanent discontinuation of CDK4/6i.