The FDA has granted breakthrough therapy status to ribociclib (LEE011, Novartis), in combination with letrozole, for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2–) advanced or metastatic breast cancer. Ribociclib is a selective cyclin-dependent kinase (CDK4/6) inhibitor. These proteins, when overactivated in a cell, can enable cancer cells to grow and divide too quickly.
According to the FDA, a breakthrough therapy designation is intended to expedite the development and review of potential new medications that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint.
Ribociclib has been studied in nonclinical models and is being evaluated in combination with additional endocrine agents as part of the MONALEESA (Mammary ONcology Assessment of LEE011’s Efficacy and SAfety) clinical trial program. Ribociclib is not approved for any indication in any market at this time.
The FDA’s breakthrough therapy designation was based primarily on positive results from the phase 3 MONALEESA-2 trial of ribociclib in combination with letrozole in postmenopausal women with HR+/HER2– advanced breast cancer who had received no prior therapy for their advanced disease. This randomized, double-blind, placebo-controlled, global registration study met its primary endpoint of clinically meaningful improvement in progression-free survival at a preplanned interim analysis.
MONALEESA-3 is evaluating ribociclib in combination with fulvestrant compared with fulvestrant alone in men and postmenopausal women with HR+/HER2– advanced breast cancer who have received no or a maximum of one prior endocrine therapy. The study is fully enrolled.
MONALEESA-7 is investigating ribociclib in combination with endocrine therapy and goserelin compared with endocrine therapy and goserelin alone in premenopausal women with HR+/HER2– advanced breast cancer who have not received endocrine therapy. MONALEESA-7 is fully enrolled and is the only phase 3 study that has focused on premenopausal and perimenopausal women with advanced breast cancer.
Up to one-third of patients with early-stage breast cancer will subsequently develop metastatic disease. Advanced breast cancer comprises locally advanced disease (stage 3) and metastatic disease (stage 4).Survival rates for women with advanced breast cancer are lower than those for women with earlier-stage disease. The five-year relative survival rate for stage-3 breast cancer is approximately 72%, whereas metastatic (stage 4) breast cancer has a five-year relative survival rate of approximately 22%.
Source: Novartis; August 3, 2016.