Novartis revealed that the European Commission has endorsed Kisqali (ribociclib) alongside an aromatase inhibitor for the adjuvant management of hormone receptor (HR)-positive, HER2-negative early breast cancer at elevated risk of recurrence.
This endorsement arises from the pivotal phase III NATALEE study, which involved a wide range of HR+/HER2- stage II and III early breast cancer patients, including those without nodal involvement. The trial unveiled a substantial and clinically significant 25.1% reduction (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006) in the likelihood of disease relapse with the combination of adjuvant Kisqali and endocrine therapy, compared to endocrine therapy alone. The invasive disease-free survival advantage was notably observed across all patient demographics.
“For numerous patients diagnosed with stage II or III HR+/HER2- early breast cancer, despite undergoing endocrine therapy, the risk of recurrence remains persistently high, even years later,” stated Dr. Michael Gnant, Professor of Surgery at the Medical University of Vienna and president of the Austrian Breast and Colorectal Study Group. “This approval signifies a promising development for Europe’s early breast cancer community, granting physicians an expanded option to aid in lessening recurrence risks within a more extensive patient demographic.”
Moreover, Dr. Michael Untch, head of the Clinic for Gynecology and Obstetrics, and Director of the Interdisciplinary Breast Cancer Center at Helios Klinikum Berlin-Buch, remarked: “Introducing a new treatment pathway into the HR+/HER2- early breast cancer treatment landscape is uplifting news for both healthcare providers and their patients, notably those at risk due to node-negative disease. Ribociclib now stands to assist numerous individuals in mitigating the odds of cancer revisiting.”
Being the most frequently diagnosed cancer in Europe, around 70% of breast cancer cases are identified in the early stages. Despite existing treatments, individuals with stage II and III HR+/HER2- early breast cancer continue facing long-term recurrence risks, commonly progressing to incurable advanced stages.
“Managing the recurrence risk is a long-term ordeal for those coping with breast cancer. Patients deserve access to treatment solutions that substantially lower the chances of cancer returning, offering them much-needed peace of mind,” expressed Dr. Iris Zemzoum, President of Europe at Novartis. “We take immense pride in this approval, which targets essential unmet needs and enhances health outcomes for a wider range of patients throughout Europe.”
This update follows the recent approval by the US Food and Drug Administration for Kisqali in early breast cancer patients, and its recommendation as a top-tier preferred adjuvant treatment by the National Comprehensive Cancer Network Guidelines. Kisqali has also attained the highest score (A) on the European Society for Medical Oncology’s Clinical Benefit Scale for early breast cancer treatment.
Globally, the regulatory evaluation of Kisqali in early breast cancer is ongoing. Following recent disclosures at ESMO 2024, Novartis will persist in assessing NATALEE patients for prolonged outcomes, such as overall survival.
NATALEE is an international phase III multi-center, randomized, open-label study focussing on the efficacy and safety of Kisqali combined with endocrine therapy as an experimental adjuvant treatment versus endocrine therapy solely in stage II and III HR+/HER2- early breast cancer patients, executed in partnership with TRIO. The adjuvant endocrine therapy in the study’s treatment segments involved a non-steroidal aromatase inhibitor and, if relevant, goserelin. The core endpoint of NATALEE is invasive disease-free survival, as per the Standardized Definitions for Efficacy End Points (STEEP) criteria. The trial comprised 5,101 adult HR+/HER2- early breast cancer patients across 20 countries.
Kisqali, a selective cyclin-dependent kinase inhibitor, decelerates cancer development by targeting over-active proteins called cyclin-dependent kinases 4 and 6 (CDK4/6), which facilitate rapid cancer cell division. Accurately targeting CDK4/6 is crucial in controlling uncontrolled cancer cell replication.
Approved by regulatory bodies across over 100 countries worldwide, including the US FDA and European Commission, Kisqali is sanctioned in the US alongside an aromatase inhibitor for the adjuvant or treatments of HR+/HER2- stage II and III early breast cancer at substantial relapse risk; also in HR+/HER2- advanced or metastatic breast cancer as an initial endocrine treatment or post-endocrine progression. In Europe, Kisqali, combined with an aromatase inhibitor, is endorsed for patients with HR+/HER2- early breast cancer at high recurrence risk. In pre- or perimenopausal women, or in men, it should be paired with a luteinizing hormone-releasing hormone (LHRH) agonist; Kisqali is approved in metastatic cases with either an aromatase inhibitor or fulvestrant as initial or post-endocrine progression treatment.
Kisqali is the exclusive CDK4/6 inhibitor suggested for both node-positive and high-risk node-negative cases (such as large tumors or particular grades) in early-stage breast cancer treatment. This combination has received an “A” ranking on the ESMO-Magnitude of Clinical Benefit Scale.
In metastatic settings, Kisqali has persistently demonstrated significant survival benefits across three phase III trials. The NCCN Guidelines endorse ribociclib as the sole Category 1 preferred CDK4/6 inhibitor for initial HR+/HER2- metastatic breast cancer treatment with an aromatase inhibitor, making it the foremost choice for US prescribers. Additionally, Kisqali excels with high ratings on the ESMO scale for both pre-menopausal and post-menopausal advanced HR+/HER2- breast cancer patients.
Kisqali was conceptualized by Novartis in collaboration with Astex Pharmaceuticals.
Novartis’s over 30-year leadership in advancing scientific knowledge for breast cancer patients continues, with a focus on evolving clinical practices globally. With a robust portfolio and developmental pipeline, Novartis remains a pioneer in innovations for HR+/HER2- breast cancer, the most prevalent variant of this disease.