Advancing treatment choices: CDK4/6 inhibitor switching in HR+/HER2- metastatic breast cancer

Purpose: CDK4/6 inhibitors (CDK4/6i) use has revolutionized the treatment of hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer. The choice of a specific CDK4/6i may be influenced by adverse events (AEs). Recently, the Italian Medicines Agency (AIFA) approved the possibility of switching between CDK4/6i for unacceptable toxicity. This study explores oncologists' experiences and future perspectives on CDK4/6 inhibitor switching following this new approval. Methods: With the support of the Italian Association of Medical Oncology (AIOM), we conducted a survey among 92 oncologists to assess the impact of AIFA's approval on patient management. Results: The survey showed that 48 % of participants were not surprised regarding AIFA's decision, with 76 % of respondents believing that this opportunity would significantly influence their treatment choices, enhancing AEs management for patients. Yet, 49 % of respondents emphasized the need for more real world evidence on CDK4/6i switch safety and efficacy. 96 % of respondents reported discontinuation rates between 0% and 25 % of patients, with constipation and hematological toxicity being the most frequent treatment discontinuation reasons. The oncologists prescribing CDK4/6i switch reported that most of these patients were in first line treatment (85 %) and the most common second CDK4/6i most frequently initiated was palbociclib (69 %), then abemaciclib (17 %) and ribociclib (14 %). Among those who started the second CDK4/6i at full dosage, 66 % of patients didn't require a dose reduction. Conclusion: Our survey highlights the importance of allowing CDK4/6i switching, thus likely prompting oncologists to adapt their treatment choices, leading to better AEs management for improving patients’ outcome.