Kisqali delivers consistently superior overall survival MONALEESA-3 trial demonstrates more life for postmenopausal HR+/HER2- advanced breast cancer patients.- Novartis

Novartis announced results from the MONALEESA-3 trial which showed Kisqali (ribociclib) achieved statistically significant improvement in overall survival (OS). This is the second Phase III trial in which Kisqali combination therapy met the secondary endpoint of overall survival at the pre-planned interim analysis. MONALEESA-3 evaluated efficacy and safety of Kisqali plus fulvestrant in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. These data will be presented as a late-breaker oral presentation in the Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2019.

"Seen now in two Phase III trials, ribociclib consistently and significantly prolongs life among premenopausal and postmenopausal women, and in combination with an aromatase inhibitor and fulvestrant. These results arm oncologists with more evidence to make a confident treatment choice for their hormone receptor-positive metastatic breast cancer patients," said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center.

Kisqali in combination with fulvestrant met its secondary endpoint of overall survival, demonstrating a statistically significant improvement in survival with a 28% reduction in risk of death (median OS not reached vs. 40.0 months; HR=0.724; 95% CI: 0.568-0.924; p=0.00455). The significant extension in survival met the early efficacy stopping criteria at a pre-specified interim analysis. At 42 months, estimated rates of survival were 58% for Kisqali combination treatment and 46% for fulvestrant alone. Results in the first-line and second-line subgroups, including in patients who relapsed within 12 months of adjuvant treatment, were consistent with the overall MONALEESA-3 patient population.

Median PFS in the first-line was also reached at this analysis and demonstrated that Kisqali in combination with fulvestrant has a median PFS of 33.6 months compared to 19.2 months in the placebo arm (HR=0.546; 95% CI: 0.415-0.718). Additionally, the need for chemotherapy was delayed in all patients who were prescribed Kisqali plus fulvestrant (HR=0.696; 95% CI: 0.551-0.879).

"The remarkable results from MONALEESA-3 and MONALEESA-7 make Kisqali the CDK4/6 inhibitor with consistently superior overall survival," said Susanne Schaffert, PhD, President, Novartis Oncology. "In nearly 25 years, the five-year survival rates in HR+ metastatic breast cancer have improved by less than 5%. We are committed to helping give these women more life and are reimagining a world where metastatic breast cancer becomes a curable disease."

MONALEESA-3 is the largest trial to evaluate a CDK4/6 inhibitor plus fulvestrant as initial therapy in postmenopausal women (N=726). The trial included women with no prior endocrine therapy, including those diagnosed de novo, women who relapsed within 12 months of adjuvant therapy and women who progressed on endocrine therapy for advanced disease. The most common grade 3/4 adverse events of special interest observed in this analysis in patients who received Kisqali plus fulvestrant compared to fulvestrant alone were neutropenia (57.1% vs 0.8%), hepatobiliary toxicity (13.7% vs 5.8%), QTc prolongation (3.1% vs 1.2%), respiratory disorders (2.3% vs 3.3%) and interstitial lung disease (0.2% vs 0%).