From the Guidelines
Ribociclib can be given in the neoadjuvant setting for hormone receptor-positive (HR+), HER2-negative breast cancer patients, typically in combination with endocrine therapy, as evidenced by the NATALEE trial 1. The standard regimen involves ribociclib 600 mg once daily for 21 days followed by a 7-day break (28-day cycle), alongside an aromatase inhibitor such as letrozole 2.5 mg daily or an alternative endocrine therapy. Treatment duration in the neoadjuvant setting is usually 4-6 months before surgery. This approach is most appropriate for postmenopausal women or premenopausal women with ovarian suppression who have larger tumors that might benefit from downstaging before surgery. Ribociclib works by inhibiting cyclin-dependent kinases 4 and 6 (CDK4/6), which prevents cell cycle progression and tumor growth in hormone-dependent breast cancer. Regular monitoring is essential during treatment, including complete blood counts, liver function tests, and ECGs to monitor for QT interval prolongation, as ribociclib can cause neutropenia, hepatotoxicity, and cardiac conduction abnormalities. Some key points to consider when using ribociclib in the neoadjuvant setting include:
- Patient selection: HR+, HER2-negative breast cancer patients with larger tumors that might benefit from downstaging before surgery.
- Treatment duration: 4-6 months before surgery.
- Monitoring: Regular complete blood counts, liver function tests, and ECGs to monitor for potential side effects.
- Combination therapy: Ribociclib is typically used in combination with endocrine therapy, such as an aromatase inhibitor. The NATALEE trial 1 demonstrated a statistically significant improvement in invasive disease-free survival with the addition of ribociclib to adjuvant endocrine therapy, supporting its use in the neoadjuvant setting. However, it is essential to weigh the potential benefits and risks of ribociclib in each individual patient, considering factors such as tumor size, patient age, and overall health status. In terms of specific patient populations, ribociclib may be particularly beneficial for postmenopausal women or premenopausal women with ovarian suppression who have high-risk disease, as defined by factors such as tumor size, grade, and lymph node involvement. Overall, ribociclib is a valuable treatment option for HR+, HER2-negative breast cancer patients in the neoadjuvant setting, and its use should be considered in conjunction with endocrine therapy and careful patient monitoring.
From the Research
Neoadjuvant Use of Ribociclib
- Ribociclib can be given in the neoadjuvant setting for patients with hormone receptor-positive, HER2-negative early stage breast cancer, specifically those with luminal B subtype 2.
- The CORALLEEN trial demonstrated that neoadjuvant ribociclib plus letrozole could achieve molecular downstaging of the disease in some patients with high-risk, early stage, hormone receptor-positive, HER2-negative breast cancer 2.
- The NEOLETRIB trial is currently evaluating the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting 3.
Patient Selection
- Patients with hormone receptor-positive, HER2-negative breast cancer, particularly those with high-risk disease, may benefit from neoadjuvant ribociclib therapy 2, 4.
- The use of CDK 4/6 inhibitors, such as ribociclib, may be useful to boost outcomes in high-risk patients with HR+ BC, but data are still emerging 4.