Positive Efficacy Results Reported for Breast Cancer Drug Ribociclib

Phase 3 study halted early after drug improves progression-free survival

The independent data monitoring committee for a pivotal phase 3 breast-cancer trial of ribociclib (LEE011, Novartis), a cyclin-dependent kinase inhibitor, has recommended stopping the trial early after results of a preplanned interim analysis showed that the study had met the primary endpoint of a clinically meaningful improvement in progression-free survival (PFS). The news puts ribocilcib on track to compete with Pfizer’s blockbuster drug palbociclib (Ibrance), according to a Reuters report.

The MONALEESA-2 (Mammary Oncology Assessment of LEE011’s Efficacy and SAfety-2) trial was evaluating ribociclib in combination with letrozole, compared with letrozole alone, in postmenopausal women who had received no prior therapy for hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2–) advanced breast cancer. The global study stratified 668 patients by the presence of liver and/or lung metastases. The patients received ribociclib 600 mg per day (three weeks on and one week off) or placebo in combination with letrozole 2.5 mg per day, per the approved label. The study’s primary endpoint was PFS. Secondary endpoints included overall survival, the overall response rate, the clinical benefit rate, health-related quality of life, safety, and tolerability.

As a cyclin-dependent kinase inhibitor, ribociclib belongs to the same drug class as palbociclib and looks set to be second to market in that category, ahead of Eli Lilly’s abemaciclib, according to analysts. Ribociclib helps slow the progression of cancer by inhibiting two proteins, cyclin- dependent kinase 4 and 6 (CDK4/6). These proteins, when overactivated in cells, can enable cancer cells to grow and divide too quickly.

Ribociclib has been studied in nonclinical models and is currently being evaluated in combination with additional endocrine agents as part of the MONALEESA clinical trial program. Ribociclib is not approved for any indication in any market at this time.

The MONALEESA-3 trial 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 MONALEESA-7 trial 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 previously received endocrine therapy.

Ribociclib was developed by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals.

Advanced breast cancer comprises locally advanced breast cancer (stage III) and metastatic breast cancer (stage IV). Locally advanced breast cancer occurs when the cancer has spread to lymph nodes and/or other tissue in the area of the breast, but not to distant sites in the body. Metastatic breast cancer is the most serious form of the disease.

HR+/HER2– advanced breast cancer is the most common type of advanced breast cancer, with an estimated 220,000 women diagnosed globally each year. HR+ advanced breast cancer is a group of cancers that express receptors for certain hormones, such as estrogen and progesterone. Cancer cell growth can be driven by these hormones.

Sources: Novartis; May 18, 2016; and Reuters; May 18, 2016.