Novartis Kisqali Cuts Death Risk 19.1% in NATALEE Breast Cancer Trial

Novartis on October 23, 2026 announced results from the six-year follow-up analysis of the Phase III NATALEE trial, reporting positive, clinically meaningful overall survival data with Kisqali (ribociclib) plus endocrine therapy compared with endocrine therapy alone in patients with HR+/HER2- early breast cancer at high risk of recurrence. According to the company’s announcement, Kisqali plus endocrine therapy reduced the risk of death by nearly 20% (19.1%) compared with endocrine therapy alone, with a hazard ratio of 0.809 and a 95% confidence interval of 0.661-0.989, and the overall survival benefit was consistent across all key subgroups. The late-breaking results will be presented at the European Society for Medical Oncology Annual Meeting 2026.

The study covered the broadest early breast cancer population of patients with stage II and III HR+/HER2- disease at high risk of recurrence, including those with high-risk node-negative (N0) disease and all node-positive patients, the company said. The presentation citation in the release lists the data as presented at the European Society for Medical Oncology Congress on October 23-27, 2026, in Madrid, Spain.

Six-Year Efficacy and Safety Results

Patients in the analysis had been off Kisqali for a median of three years (38 months) and had passed the five-year protocol-specified endocrine therapy duration, according to the release. The absolute benefit in invasive disease-free survival increased from 4.1% at five years to 5.3% at six years, with a hazard ratio of 0.741 (95% confidence interval 0.646-0.849), and the company said benefit was observed years after treatment completion.

According to the release, fewer patients treated with Kisqali plus endocrine therapy experienced metastatic recurrence compared with endocrine therapy alone, and the absolute overall survival difference increased from 1.2% at five years to 2.1% at six years. Breast cancer-specific survival showed an approximately 30% reduction in the risk of breast cancer-specific death (hazard ratio 0.709; 95% confidence interval 0.559-0.890), which the company described as supportive of the overall survival benefit; the absolute breast cancer-specific survival benefit was 1.5% at five years and 2.6% at six years. Distant disease-free survival showed a hazard ratio of 0.744 (95% confidence interval 0.646-0.858), with absolute benefit of 3.7% at five years and 4.9% at six years, while distant recurrence-free survival showed a hazard ratio of 0.738 (95% confidence interval 0.631-0.846), with absolute benefit of 3.5% at five years and 4.4% at six years.

“The NATALEE six-year data clearly demonstrate a clinically meaningful improvement in overall survival with ribociclib plus endocrine therapy,” said Dennis J. Slamon, MD, Chief of the Division of Hematology/Oncology at the UCLA Department of Medicine.

“The clinically meaningful overall survival benefit observed in NATALEE underscores Kisqali as a standard of care for eligible patients and its foundational role in early breast cancer treatment,” said Andrea Myers, Global Head, Oncology Development, Novartis, Ad Interim. Myers said the findings demonstrate the value of combining a CDK4/6 inhibitor with endocrine therapy in the broadest population of patients at high risk of recurrence, including those with high-risk node-negative disease and all node-positive patients.

With longer follow-up, the safety profile remained consistent with previous analyses and no new safety signals were observed, the company said. Overall rates of secondary primary malignancies were 3.0% with Kisqali plus endocrine therapy and 3.3% with endocrine therapy alone; secondary primary malignancies leading to death were 0.2% in both arms.

Jean A. Sachs, Chief Executive Officer of Living Beyond Breast Cancer, said in the release that for people diagnosed with early breast cancer who face a higher risk of recurrence, meaningful long-term overall survival data support shared decision-making conversations with their medical teams.

NATALEE Trial Design and Kisqali Regulatory Standing

NATALEE is a global Phase III, multi-center, randomized, open-label trial evaluating Kisqali with endocrine therapy as an adjuvant treatment versus endocrine therapy alone in patients with stage II and III HR+/HER2- early breast cancer, conducted in collaboration with TRIO. A total of 5,101 adult patients across 20 countries were randomized. Adjuvant endocrine therapy in both treatment arms consisted of a non-steroidal aromatase inhibitor (anastrozole or letrozole) plus goserelin, if applicable, and the trial’s primary endpoint is invasive disease-free survival as defined by the Standardized Definitions for Efficacy End Points criteria.

Kisqali is a selective cyclin-dependent kinase inhibitor that helps slow the progression of cancer by inhibiting two proteins, cyclin-dependent kinase 4 and 6 (CDK4/6), which when over-activated enable cancer cells to grow and divide quickly, according to the company. Novartis said Kisqali has been approved as a breast cancer treatment by regulatory authorities in more than 100 countries, including the US Food and Drug Administration and the European Commission. In the United States, Kisqali is indicated in combination with an aromatase inhibitor as adjuvant treatment for adults with HR+/HER2- stage II and III early breast cancer at high risk of recurrence, and as initial endocrine therapy for adults with HR+/HER2- advanced or metastatic breast cancer; it is also approved in the metastatic setting in combination with fulvestrant as initial endocrine therapy or following disease progression on endocrine therapy. In the European Union, Kisqali is approved in combination with an aromatase inhibitor for the adjuvant treatment of patients with HR+/HER2- early breast cancer at high risk of recurrence, and for women with HR+/HER2- locally advanced or metastatic breast cancer in combination with either an aromatase inhibitor or fulvestrant, as initial endocrine therapy or following disease progression on prior endocrine therapy. In pre- or peri-menopausal women, the endocrine therapy should be combined with a luteinizing hormone-releasing hormone agonist.

In early breast cancer, Kisqali is the only CDK4/6 inhibitor recommended by the NCCN Guidelines for breast cancer as Category 1 preferred both for all node-positive disease and for patients with no nodal involvement who have high-risk disease characteristics, such as tumor size greater than 5 cm, or tumors sized 2 to 5 cm that are either Grade 2 with high genomic risk or Ki-67 of at least 20%, or Grade 3, the company said. In the metastatic setting, the NCCN Guidelines recommend Kisqali as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of HR+/HER2- metastatic breast cancer in combination with an aromatase inhibitor. Kisqali has also achieved the highest score (A) on the ESMO Magnitude of Clinical Benefit Scale for early breast cancer, and scores of four out of five in specified first-line advanced breast cancer settings, according to the release.

Novartis said Kisqali is the only CDK4/6 inhibitor to demonstrate statistically significant overall survival benefit across three randomized controlled trials (MONALEESA-2, MONALEESA-3, and MONALEESA-7) in metastatic breast cancer. Approvals of Kisqali in early breast cancer remain ongoing worldwide, including a recent approval from China’s National Medical Products Administration, the company said. Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals.