On September 9, 2022 Novartis reported results from a new pooled exploratory analysis across the entire MONALEESA Phase III program, confirming nearly one year of additional overall survival (OS) benefit in a subgroup of patients with aggressive forms of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer (aBC)1 (Press release, Novartis, SEP 9, 2022, View Source [SID1234619328]). This subgroup analysis found that patients with visceral metastases—including liver metastases and multiple metastatic sites, which are typically associated with a poor prognosis—who were treated with Kisqali (ribociclib) plus endocrine therapy in the first-line setting, achieved a median OS of 62.7 months compared to 52.1 months for those treated with endocrine therapy alone (HR=0.79; 95% CI: 0.65-0.97)1. Data from this analysis will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Paris, France.
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"Patients who have visceral metastases typically have a worse prognosis and often demonstrate resistance to treatment, so as a clinician it is encouraging to see significant survival benefit with ribociclib in the first-line setting in patients with more aggressive disease," said Denise A. Yardley, MD, Senior Investigator, Breast Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, USA. "Ribociclib is the only CDK4/6 inhibitor to show a consistent overall survival benefit in combination with endocrine therapy, while also maintaining quality of life across the Phase III program."
Those with liver metastases on Kisqali plus endocrine therapy in the first-line achieved 44.2 months median OS compared to 38.1 months for those on endocrine therapy alone (HR=0.77; 95% CI: 0.55-1.07). For patients with visceral metastases in three or more organs, first-line
treatment with Kisqali-endocrine therapy achieved 57.7 months median OS compared to 49.3 months for those on endocrine therapy alone (HR=0.81; 95% CI: 0.63-1.03)1.
"The goal for advanced breast cancer treatment is to help people live longer, and we are proud that Kisqali continues to deliver a significant survival benefit while also maintaining quality of life, even for those with harder-to-treat disease," said Jeff Legos, Executive Vice President, Global Head of Oncology and Hematology at Novartis. "We are committed to demonstrating what makes Kisqali a unique CDK4/6 inhibitor, thus providing patients and oncologists confidence in this therapeutic option."
HARMONIA head-to-head CDK4/6 inhibitor trial design
Also at ESMO (Free ESMO Whitepaper), the trial design will be presented for HARMONIA, the first prospective, head-to-head Phase III trial of CDK4/6 inhibitors being conducted in collaboration with SOLTI Innovative Cancer Research, to evaluate Kisqali vs. Ibrance* (palbociclib) for patients with advanced HR+/HER2-, HER2-enriched subtype, ultimately exploring what makes Kisqali unique at a molecular level13. HARMONIA seeks to test if Kisqali improves the course of HR+/HER2- aBC by changing tumor biology to enable a better response to endocrine therapy as compared to Ibrance*, and could further substantiate differences seen among these CDK4/6 inhibitors. HER2-enriched is an intrinsic subtype associated with a very poor prognosis and endocrine-resistance, as compared to luminal disease. The global, multicenter, randomized, open-label, Phase III study has a primary outcome of progression-free survival (PFS), and secondary outcomes include OS and PFS2. HARMONIA is currently ongoing with an anticipated enrollment of 456 patients.
About Kisqali (ribociclib)
Kisqali is the only CDK4/6 inhibitor with proven overall survival benefit across all its three pivotal Phase III advanced breast cancer trials2-12, and is recognized by the National Comprehensive Cancer Network (NCCN) guidelines as the only CDK4/6 inhibitor with overall survival benefit in first-line HR+/HER2- advanced breast cancer14. Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line premenopausal patients with HR+/HER2- advanced breast cancer15. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6i, received a score of four out of five for postmenopausal patients with HR+/HER2- advanced breast cancer treated in the first line16.
Kisqali has been approved in more than 95 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission, for the treatment of women with HR+/HER2- advanced or metastatic breast cancer in combination either with an aromatase inhibitor or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy13,17. Kisqali in combination with fulvestrant is approved as initial endocrine-based therapy or following disease progression on endocrine therapy in men by the FDA17.
Novartis is committed to continuing to study Kisqali in breast cancer. NATALEE is a large 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)18. Additionally, Novartis is collaborating with the Akershus University Hospital in Norway on the NEOLETRIB trial, a neoadjuvant Phase II trial studying the effects of Kisqali in HR+/HER2- early breast cancer and to discover the potentially unique underlying mechanism of action19.
Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.
Please see full Prescribing Information for Kisqali, available at www.Kisqali.com.
About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with metastatic breast cancer.