The US Food and Drug Administration (FDA) has approved ribociclib plus an aromatase inhibitor for first-line endocrine-based treatment of pre/perimenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. In addition, ribociclib plus fulvestrant was approved for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer as initial or second-line endocrine-based therapy.1
This marks the first FDA-approval granted after the implementation of 2 pilot programs — the Real-Time Oncology Review and Assessment Aid — that seek to improve the efficiency of oncologic drug development and review, as well increase the standards of safety and efficacy.2,3
The FDA based its approval on the results of the phase 3 MONALEESA-2 (ClinicalTrials.gov Identifier: NCT01958021), MONALEESA-3 (ClinicalTrials.gov Identifier: NCT02422615), and MONALEESA-7 (ClinicalTrials.gov Identifier: NCT02278120) studies.4
In the MONALEESA-7 study, researchers randomly assigned 495 endocrine therapy-naive, pre/perimenopausal women with HR+/HER2- advanced breast cancer to receive ribociclib plus an aromatase inhibitor and goserelin or placebo plus an aromatase inhibitor and goserelin. Patients in the ribociclib arm had an estimated median progression-free survival (PFS) of 27.5 months compared with 13.8 months among patients assigned to the placebo arm (hazard ratio [HR], 0.569; 95% CI, 0.436-0.743).
In the MONALEESA-3 study, 726 postmenopausal patients with HR+/HER2- advanced breast cancer, who never received or received only one previous line of endocrine therapy, were randomly assigned to the ribociclib plus fulvestrant group or to fulvestrant alone group. After a median follow-up of 16.5 months, patients in the ribociclib arm had an estimated median PFS of 20.5 months compared with 12.8 months among those assigned to fulvestrant alone (HR, 0.593; 95% CI, 0.480-0.732; P < .0001).
The investigators for the MONALEESA-2 study assessed the efficacy of ribociclib plus letrozole versus letrozole alone among never-treated patients with HR+/HER2- advanced breast cancer, for which the data led to initial FDA approval. Overall survival analysis is ongoing.
The most frequently reported adverse events occurring in 20% or more of patients included alopecia, diarrhea, neutropenia, leukopenia, nausea, vomiting, constipation, infections, fatigue, headache, rash, and cough.
- FDA expands ribociclib indication in HR-positive, HER2-negative advanced or metastatic breast cancer [press release]. Silver Springs, MD: US Food and Drug Administration; Updated July 18, 2018. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm613803.htm. Accessed July 18, 2018.
- US Food and Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OCE/ucm612927.htm. Updated July 11, 2018. Accessed July 18, 2018.
- US Food and Drug Administration. Assessment Aid Pilot Project. https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OCE/ucm612923.htm. Updated July 11, 2018. Accessed July 18, 2018.
- Novartis Kisqali® now first and only CDK4/6 inhibitor indicated in US as first-line therapy specifically for premenopausal women; and as initial therapy with fulvestrant in postmenopausal women [press release]. Basel, Switzerland: Novartis; Updated July 18, 2018. http://hugin.info/134323/R/2205983/857280.pdf. Accessed July 18, 2018.