Novartis Kisqali shows overall survival benefit in HR+/HER2- advanced breast cancer with consistent findings in patients with more aggressive disease.

Novartis announced a new exploratory subgroup analysis of the Phase III MONALEESA-3 and MONALEESA-7 trials, to be presented during the ASCO20 Virtual Scientific Program, reinforcing the overall survival (OS) benefit of Kisqali (ribociclib) . In this subgroup analysis, Kisqali plus endocrine therapy increased OS compared to endocrine therapy alone among women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer with visceral metastases, consistent with the benefit seen in the overall study populations.

“The analysis, looking across two Phase III trials, supports the use of Kisqali in the first-line setting regardless of menopausal status or metastatic location,” said Denise Yardley, MD, Principal Investigator, Sarah Cannon Research Institute. “Patients with visceral metastases generally face worse prognosis and a higher risk for treatment resistance, so the consistent overall survival results with Kisqali combination therapy for these patients is compelling.”

In the MONALEESA trials , where Kisqali was studied in premenopausal women in combination with NSAI plus goserelin (MONALEESA-7) and in postmenopausal women in combination with fulvestrant (MONALEESA-3), approximately 60% of the participants had visceral metastases (excluding visceral crisis), reflective of real-world clinical practice. In these patients, Kisqali in combination with endocrine therapy showed a 30% reduction in the risk of death in MONALEESA-7 [median OS of not evaluable (NE) vs. 39.9 months with NSAI plus goserelin; HR= 0.698 (95% CI: 0.462-1.054)] and a 20% reduction in the risk of death in MONALEESA-3 [median OS of 41.0 vs. 39.4 months with fulvestrant; HR=0.804 (95% CI: 0.596-1.083)]. In patients with liver metastases, Kisqali combination therapy showed a 47% reduction in the risk of death in MONALEESA-7 [median OS of NE vs. 33.6 months with NSAI plus goserelin; HR=0.531 (95% CI: 0.321-0.877)] and a 37% reduction in the risk of death in MONALEESA-3 [median OS of 36.1 vs. 24.1 months with fulvestrant; HR=0.629 (95%CI: 0.421-0.942)]. The adverse events were consistent with the overall populations.

Additional Kisqali data presented during the ASCO20 Virtual Scientific Program include :
• An oral presentation on the largest pooled biomarker dataset of any CDK4/6 inhibitor in advanced breast cancer to date across a targeted panel of approximately 550 genes related to cancer and signaling pathways. The analysis identifies key potential gene alterations and their associations with response or resistance to Kisqali across all three MONALEESA trials.
• Updated results from CompLEEment-1, a Phase IIIb single-arm trial of 3,246 patients in first-line setting evaluating Kisqali plus letrozole in an expanded and diverse population closely resembling real-world clinical practice. Results were consistent with those observed in the MONALEESA trials, including median time to progression 27.1 months (95% CI: 25.7-NE) and overall response rate 43.6% (95% CI: 41.5-45.8%). The most common AEs were neutropenia, nausea and fatigue. Treatment-related AEs led to discontinuation in 12.9% of patients.
• A retrospective study using real-world data assessing the economic burden of neutropenia, the most common adverse event following administration of CDK4/6 inhibitors. Neutropenia was reported in 38 patients (25%) in the palbociclib group and 25 patients (17%) in the Kisqali group. Similar rates of neutropenia were observed for grades 1/2 and 4, however, a numerical difference was observed for grade 3: palbociclib 35% vs. Kisqali 26%.

Kisqali is approved for use in more than 75 countries around the world, including the United States and European Union member states. Kisqali has shown statistically significant overall survival benefit in two Phase III trials with two distinct patient populations.