Ribociclib Granted FDA Priority Review for First-Line Treatment of Hormone Receptor–Positive/HER2-Negative Advanced Breast Cancer
On November 1, the U.S. Food and Drug Administration (FDA) accepted a New Drug Application (NDA) for filing and granted Priority Review for ribociclib (LEE011) as first-line treatment of postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with letrozole. The NDA is based on a comprehensive clinical package, including results of the phase III MONALEESA-2 trial.
The MONALEESA-2 trial, which was presented at the European Society for Medical Oncology (ESMO) 2016 Congress (Abstract LBA1) and published simultaneously by Hortobagyi et al in The New England Journal of Medicine, showed that ribociclib plus letrozole reduced the risk of progression or death by 44% (hazard ratio [HR] = 0.556, 95% confidence interval [CI] = 0.429–0.720; P = .00000329) over letrozole alone, significantly extending progression-free survival across all patient subgroups.
The manufacturer of ribociclib, Novartis, also announced that the European Medicines Agency (EMA) has accepted for review the marketing authorization application for ribociclib plus letrozole in the same patient population.
“These regulatory milestones, along with the FDA Breakthrough Therapy designation granted in August, underscore the need for new treatment options for women living with hormone receptor–positive, HER2-negative advanced breast cancer,” said Bruno Strigini, CEO, Novartis Oncology. “Priority Review allows a shorter review period compared with FDA standard review in the United States, helping us to potentially bring ribociclib plus letrozole to patients more quickly. We also are working diligently with the EMA and other health authorities to bring this treatment to patients around the world as fast as possible.”
FDA Priority Review designation requires the agency to take action on an application within 6 months of its filing date compared to 10 months under standard review.
About Ribociclib
Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when overactivated in a cell, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring cancer cells do not grow uncontrollably.
Ribociclib is not approved for any indication in any market at this time.
MONALEESA Clinical Trial Program
Novartis is continuing to assess ribociclib through the robust MONALEESA clinical trial program, which includes MONALEESA-2, MONALEESA-3, and MONALEESA-7. These trials are evaluating ribociclib in multiple endocrine therapy combinations across a broad range of patients, including men and premenopausal women.
MONALEESA-2 is a phase III randomized, double-blind, placebo-controlled, multicenter global registration trial to evaluate the safety and efficacy of ribociclib in combination with letrozole compared to letrozole alone in postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer who received no prior therapy for their advanced breast cancer.
The trial randomized 668 patients in a 1:1 ratio stratified by the presence of liver and/or lung metastases at 223 clinical trial sites globally. Patients received ribociclib 600 mg/d (3 weeks on, 1 week off) or placebo, in combination with letrozole 2.5 mg/d.
The primary endpoint of the trial was progression-free survival. Secondary endpoints included overall survival, overall response rate, clinical benefit rate, health-related quality of life, safety, and tolerability.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
