Combination Therapy with Ribociclib and Nonsteroidal Aromatase Inhibitors for HR-Positive, HER2-Negative Breast Cancer
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on April 19th, 2024
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Breast cancer tumors that express hormone receptors (HR) but not epidermal growth factor receptor 2 (HER2) constitute the most prevalent type of breast cancer. Ribociclib, an agent that inhibits cyclin-dependent kinases 4 and 6, has shown efficacy in suppressing tumor progression and is commonly used in the treatment of advanced-stage breast cancer. Consequently, a study was conducted to evaluate the potential of Ribociclib in treating early-stage HR-positive, HER2-negative breast cancer.
The phase 3 clinical trial recruited a total of 5101 patients diagnosed with breast cancer expressing hormone receptors (HR) but lacking human epidermal growth factor receptor 2 (HER2). Among the cohort, approximately 20% had stage IIa disease, another 20% had stage IIb, and the remaining 60% had stage III disease. All participants underwent a 60-month treatment regimen consisting of either oral letrozole at a daily dose of 2.5 mg or oral anastrozole at a daily dose of 1 mg, both nonsteroidal aromatase inhibitors (NSAIs). Additionally, half of the participants were randomly assigned to receive oral ribociclib, a CDK4/6 inhibitor, at a daily dose of 400 mg, administered on a 4-week cycle with 3 weeks of treatment followed by 1 week without treatment, for a total of 36 months. After 3 years, researchers concluded that combining NSAIs with ribociclib reduced the risk of invasive disease and death by 25% in patients with HR-positive, HER2-negative breast cancer compared to those treated solely with NSAIs. Analysis of adverse effects revealed a significantly higher incidence of mild to severe (grade 3 and 4) adverse events in the combination therapy group. Concurrent use of ribociclib and NSAIs notably increased the risk of neutropenia, nausea, and elevated ALT and AST levels.
The phase 3 clinical trial recruited a total of 5101 patients diagnosed with breast cancer expressing hormone receptors (HR) but lacking human epidermal growth factor receptor 2 (HER2). Among the cohort, approximately 20% had stage IIa disease, another 20% had stage IIb, and the remaining 60% had stage III disease. All participants underwent a 60-month treatment regimen consisting of either oral letrozole at a daily dose of 2.5 mg or oral anastrozole at a daily dose of 1 mg, both nonsteroidal aromatase inhibitors (NSAIs). Additionally, half of the participants were randomly assigned to receive oral ribociclib, a CDK4/6 inhibitor, at a daily dose of 400 mg, administered on a 4-week cycle with 3 weeks of treatment followed by 1 week without treatment, for a total of 36 months. After 3 years, researchers concluded that combining NSAIs with ribociclib reduced the risk of invasive disease and death by 25% in patients with HR-positive, HER2-negative breast cancer compared to those treated solely with NSAIs. Analysis of adverse effects revealed a significantly higher incidence of mild to severe (grade 3 and 4) adverse events in the combination therapy group. Concurrent use of ribociclib and NSAIs notably increased the risk of neutropenia, nausea, and elevated ALT and AST levels.