May 27, 2020: “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.
“Superior overall survival with Kisqali is proven in two phase III trials, and this subgroup analysis shows that Kisqali could make a difference in survival even among patients with the most aggressive forms of advanced breast cancer,” said Susanne Schaffert, PhD, President, Novartis Oncology.
“Patients are the inspiration behind everything we do, and we will continue to pursue bold treatment advancements that help reimagine the future for people with cancer in hopes that they can live longer, and better.”
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 complement-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 the 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 the 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 a statistically significant overall survival benefit in two Phase III trials with two distinct patient populations.
Kisqali is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone.
Overall survival results from MONALEESA-7 and MONALEESA-3 were presented at ASCO 2019 and ESMO 2019 respectively, demonstrating Kisqali plus endocrine therapy significantly extends life in pre/perimenopausal or postmenopausal women with HR+/HER2- advanced breast cancer.
Overall survival follow-up is ongoing for the Phase III MONALEESA-2 trial.
Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial.
Kisqali in combination with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine-based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018.
Regulatory filings are underway with other health authorities worldwide.
Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer.
The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO).
Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.”