Ribociclib Plus Letrozole Prolongs PFS in Advanced Breast Cancer: A Secondary Analysis of MONALEESA-2
Although endocrine therapy has been the standard of care for HR+/HER2- breast cancer, cyclin-D and cyclin-dependent kinase (CDK) dysregulation-driven resistance to this treatment occurs at very high r
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First-line ribociclib plus letrozole prolonged progression-free survival (PFS) among postmenopausal patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer, according to a poster presented at the 35th Annual Chemotherapy Foundation Symposium.1
Although endocrine therapy has been the standard of care for HR+/HER2- breast cancer, cyclin-D and cyclin-dependent kinase (CDK) dysregulation-driven resistance to this treatment occurs at very high rates among patients.
In the double-blinded phase 3 MONALEESA-2 trial (ClinicalTrials.gov Identifier: NCT01958021), researchers randomly assigned 668 postmenopausal women with HR+/HER2- advanced breast cancer who had not been previously treated for advanced disease to receive ribociclib plus letrozole or placebo plus letrozole.
An interim analysis of the MONALESSA-2 study demonstrated that ribociclib plus letrozole significantly prolonged PFS compared with placebo plus letrozole. Median PFS was not reached compared with 14.7 months (hazard ratio [HR], 0.556; 95% CI, 0.429-0.720; P = .00000329) among patients treated with ribociclib and letrozole vs placebo and letrozole, respectively. Overall survival (OS) data was not mature at the time of the interim analysis.
At the time of second interim analysis, the median duration of follow-up was 26.4 months and 219 patients remained on treatment. A continued PFS benefit was observed in patients who received ribociclib plus letrozole compared with placebo plus letrozole (HR, 0.568; 95% CI, 0.457-0.704; P = 9.63 x 10-8). Analysis of the results demonstrated that patients receiving ribociclib and letrozole had a median PFS of 25.3 months (95% CI, 23.0-30.3) compared with 16.0 months (95% CI, 13.4-18.2) among patients receiving placebo plus letrozole, and 24-month PFS rates were 54.7% and 35.9%, respectively.
Prolonged PFS benefit was observed across all pre-specified patient subgroups, including ECOG status, age, de novo advanced breast cancer, and prior therapies.
OS data remained immature at the time of secondary interim analysis; median OS was not reached in the ribociclib plus letrozole arm compared with 33.0 months among patients treated with placebo plus letrozole. More patient deaths were reported in the placebo plus letrozole arm (HR, 0.746; 95% CI, 0.517-1.078; P = .059).
The overall response rate was 42.5% and 28.7% among patients receiving ribociclib plus letrozole vs placebo plus letrozole, respectively, and the clinical benefit rate was 79.9% and 73.1%, respectively.
The most frequently reported grade 3 to 4 adverse events were neutropenia, decreased neutrophil count, and leukopenia. Overall, the safety profile of ribociclib plus letrozole in this analysis remained consistent with that seen in the first interim assessment.
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- Hortobagyi GN, Burris HA< Blackwell KL, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib + letrozole in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Poster presented at: 35th Annual Chemotherapy Foundation Symposium. Poster 567.