Phase III MONALEESA-2 study shows LEE011 (ribociclib) plus letrozole significantly extended progression-free survival in HR+/HER2- breast cancer- Novartis

Results from the pivotal Phase III MONALEESA-2 study show LEE011 (ribociclib), from Novartis, plus letrozole significantly extended progression-free survival (PFS) compared to a standard of care, letrozole, as a first-line treatment in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (median PFS, 95% CI (19.3 months - not reached) vs. 14.7 months (13.0 - 16.5 months). The results demonstrate that LEE011 plus letrozole reduced the risk of death or progression by 44% over letrozole alone.

The combination significantly improved PFS across all patient subgroups, regardless of disease characteristics or demographics. More than half of women with measurable disease taking LEE011 plus letrozole saw their tumor size shrink by at least 30% (overall response rate (ORR) in patients with measurable disease = 53% vs 37%). Most adverse events in the MONALEESA-2 trial were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The data will be featured at the European Society for Medical Oncology 2016 Congress and published simultaneously online in The New England Journal of Medicine.

Comment: The MONALEESA-2 findings seem to validate the use of a selective CDK4/6 inhibitor in combination with hormonal therapy as initial treatment for HR+/HER2- advanced breast cancer. Due to the extension of PFS and clinical benefit seen with LEE011, analysis of the primary endpoint (PFS) in MONALEESA-2 was stopped early in May 2016 as recommended by the Independent Data Monitoring Committee. Follow up to measure overall survival is ongoing.