Ribociclib FDA-Approved For Additional Indications in HR+, HER2- Advanced Breast Cancer

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.

References

1. 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.
2. 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.
3. 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.
4. 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.