Novartis has announced results from the phase III MONALEESA-7 trial in premenopausal or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer demonstrating Kisqali (ribociclib) in combination with an aromatase inhibitor or tamoxifen and goserelin as initial endocrine-based therapy significantly prolonged progression-free survival (PFS) compared to endocrine therapy and goserelin alone. These data presented at a late-breaker oral presentation at the 2017 San Antonio Breast Cancer Symposium (SABCS).

Kisqali in combination with tamoxifen or an aromatase inhibitor plus goserelin demonstrated a median PFS of 23.8 months (95% CI: 19.2 months-not reached) compared to 13.0 months (95% CI: 11.0-16.4 months) for tamoxifen or an aromatase inhibitor plus goserelin (HR=0.553; 95% CI: 0.441-0.694; p<0.0001). Premenopausal women treated with Kisqali combination therapy saw a response as early as eight weeks as demonstrated by separation of the PFS curves compared to endocrine therapy alone.

"The strength of the MONALEESA-7 data is impressive and will give oncologists an important option if ribociclib is approved as treatment for this patient population as well as greater flexibility in the choice of endocrine therapy given with this agent," said Dr. Debu Tripathy, chair of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center. "Women who are premenopausal at the time of their breast cancer diagnosis tend to have more aggressive disease with poorer prognosis along with unique needs and experiences, so it is critical we determine which treatments will be most effective while also well tolerated."  

MONALEESA-7 trial evaluated Kisqali in combination with tamoxifen and an aromatase inhibitor. This is the only phase III study to evaluate a CDK4/6 inhibitor in combination with tamoxifen and establishes the safety and efficacy of Kisqali in this combination as first-line treatment for advanced breast cancer (median PFS of 22.1 vs 11.0 months; HR=0.585; 95% CI: 0.387-0.884). Kisqali in combination with an aromatase inhibitor demonstrated an additional 14 months progression-free survival over endocrine therapy alone (median PFS of 27.5 vs 13.8 months; HR=0.569; 95% CI: 0.436-0.743).  

Premenopausal women taking Kisqali benefited for a longer time until health-related quality of life (QoL) deterioration compared to those taking endocrine therapy alone. Women taking Kisqali also had a clinically meaningful improvement in pain symptoms as early as eight weeks; this improvement was sustained.  

No new safety signals were observed in the MONALEESA-7 trial; adverse events were generally consistent with those observed in MONALEESA-2, identified early and mostly managed through dose interruptions or reductions. Combination treatment with Kisqali was well tolerated with a discontinuation rate due to adverse events of 3.6% compared to 3.0% in patients who received endocrine therapy alone. The most common (>=5%) grade 3/4 adverse events in patients receiving Kisqali combination therapy compared to endocrine therapy alone were neutropenia (60.6% vs 3.6%) and leukopenia (14.3% vs 1.2%).


"We are pleased to see Kisqali combination therapy provide strong efficacy and prolonged quality of life with pain reduction in younger women, and look forward to working with health authorities to bring a new treatment option to premenopausal or perimenopausal women," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "Research in premenopausal advanced breast cancer is extremely limited as these women traditionally have been excluded from clinical trials or reduced to a subgroup in trials designed for their postmenopausal counterparts. We designed the robust MONALEESA clinical trial program to be inclusive of all women and men with HR+/HER2- advanced breast cancer."

Premenopausal breast cancer is a biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer death in women 20-59 years old.

MONALEESA-7 is a phase III randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of Kisqali in combination with tamoxifen or a non-steroidal aromatase inhibitor plus goserelin versus tamoxifen or an aromatase inhibitor plus goserelin, in premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer who had not previously received endocrine therapy for advanced disease. More than 670 women ranging from 23-58 years in age were randomized in the MONALEESA-7 trial. The first patient assessment occurred at eight weeks; separation of the PFS curves at this time was not a pre-specified endpoint of the study.