Updated results from the Phase 3 NATALEE trial reveal that Kisqali (ribociclib) significantly cut the risk of recurrence in patients with HR+/HER2- early breast cancer. Adding Kisqali to standard endocrine therapy (ET) resulted in a 28.5% reduction in invasive disease-free survival (iDFS) events compared to ET alone (HR=0.715; 95% CI: 0.609–0.840; P<0.0001), Novartis announced in a press release. This benefit was seen across the board, including in patients whose cancer hadn’t spread to the lymph nodes. Improvements continued even after the initial three years of treatment.
NATALEE enrolled more than 5,000 patients
The NATALEE trial was a large-scale international study that looked at the effectiveness of combining Kisqali with standard hormone therapy in patients with stage II and III HR+/HER2- early breast cancer. The trial involved 5,101 patients who were randomly assigned to receive either Kisqali plus hormone therapy or hormone therapy alone.
“With longer follow-up, the clinically relevant benefit of adding ribociclib to endocrine therapy continues to improve, even after the end of ribociclib treatment, for both node-positive and node-negative patients,” said Dr. Peter A. Fasching in a press release. Fasching is Professor of Translational Medicine, University Hospital Erlangen and Comprehensive Cancer Center Erlangen-EMN and NATALEE trial investigator.
According to Dr. Shreeram Aradhye, President of Development and Chief Medical Officer at Novartis, the findings further bolster the evidence that Kisqali can consistently reduce the risk of cancer recurrence in a range of patients.
NATALEE trial design and endpoints
The trial enrolled 5,101 adult patients with stage II and III HR+/HER2- EBC, randomly assigning them to receive either ribociclib (400 mg/day, 3 weeks on/1 week off for 36 months) plus standard ET or standard ET alone.
The NATALEE trial’s primary endpoint was invasive disease-free survival (iDFS), defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria. Secondary endpoints included recurrence-free survival, distant disease-free survival, and overall survival.
The trial was conducted in partnership with the Translational Research In Oncology (TRIO) group.
The NATALEE trial included a broad population of patients with HR+/HER2- EBC, reflecting the real-world clinical setting. This included both node-positive and node-negative patients.
Standard ET in the trial consisted of at least five years of a non-steroidal aromatase inhibitor (NSAI), such as letrozole or anastrozole. Premenopausal women also received goserelin, a gonadotropin-releasing hormone agonist, to suppress ovarian function.
Understanding HR+/HER2- early breast cancer
Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) is the most common breast cancer subtype, responsible for roughly 70% of all diagnoses, according to SEER data. Despite progress in treating early breast cancer (EBC), the threat of it coming back remains a major concern for many patients, even after undergoing surgery, chemotherapy, and radiation. This risk is especially high for those with larger tumors, lymph node involvement, and certain tumor biological characteristics.
Ribociclib is a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. CDK4/6 enzymes are involved in regulating cell growth and division. By selectively inhibiting these enzymes, Kisqali helps to slow or stop the proliferation of cancer cells.
The trial also demonstrated a significant improvement in DDFS for patients receiving ribociclib plus ET compared to ET alone. The hazard ratio was 0.715 (95% CI: 0.604–0.847; P<0.0001), indicating a consistent benefit in preventing distant recurrences.
Overall Survival Trend and Safety Profile
Overall Survival (OS) Trend: The study showed a trend towards improved overall survival with ribociclib plus ET (HR=0.827; 95% CI: 0.636–1.074; one-sided P=0.0766). While the OS data are not yet mature, further follow-up is planned to obtain more definitive results.
The safety profile of ribociclib remained consistent with previous studies, with no new safety signals identified.
Novartis has submitted the NATALEE trial data to the FDA and European Medicines Agency (EMA) in 2023.
The company expects a regulatory decision from the FDA in the third quarter, which would potentially expand the approved indications for Kisqali to include early breast cancer.
Filed Under: clinical trials, Drug Discovery, Oncology
