Novartis Kisqali cuts death risk by 19% in early breast cancer trial
Novartis has reported six-year follow-up data from the Phase III NATALEE trial showing that Kisqali (ribociclib) combined with endocrine therapy reduced the risk of death by 19.1% compared to endocrine therapy alone in patients with stage II and III HR+/HER2- early breast cancer at high risk of recurrence (hazard ratio 0.809; 95% CI: 0.661–0.989). The results were presented at the European Society for Medical Oncology Annual Meeting in Madrid on 23 October 2026.
Notably, patients had been off Kisqali for a median of three years at the point of analysis, having also completed the five-year protocol-specified endocrine therapy duration. Despite the absence of active treatment, clinical benefit continued to deepen over time. The absolute difference in overall survival between the two arms widened from 1.2% at five years to 2.1% at six years, and breast-cancer specific survival showed a roughly 30% reduction in the risk of breast-cancer deaths (HR=0.709; 95% CI: 0.559–0.890).
Trial data in full
Invasive disease-free survival, the primary endpoint, also improved: the absolute benefit grew from 4.1% at five years to 5.3% at six years (HR=0.741). Distant disease-free survival and distant recurrence-free survival followed a similar trajectory, with hazard ratios of 0.744 and 0.738 respectively. The safety profile at six years was consistent with earlier analyses. Rates of secondary primary malignancies were 3.0% in the ribociclib arm versus 3.3% in the endocrine-therapy-only arm, with deaths attributable to secondary malignancies at 0.2% in both groups.
Dennis Slamon, Chief of the Division of Haematology/Oncology at UCLA's Department of Medicine and a principal investigator on NATALEE, said the six-year data "clearly demonstrate a clinically meaningful improvement in overall survival" and that the findings "further strengthen the role of ribociclib in treating patients with HR+/HER2- early breast cancer at high risk of recurrence."
The NATALEE trial enrolled 5,101 adults across 20 countries, making it one of the largest adjuvant studies in this breast cancer subtype. The inclusion of high-risk node-negative patients alongside all node-positive patients distinguishes the trial's scope from some earlier CDK4/6 inhibitor studies in the early setting.
Competitive and regulatory context
Kisqali's CDK4/6 inhibitor class also includes palbociclib (Pfizer's Ibrance) and abemaciclib (Eli Lilly's Verzenio). In the early breast cancer setting, abemaciclib has established its own survival data via the monarchE trial, making the CDK4/6 inhibitor adjuvant space increasingly competitive. Novartis argues that Kisqali is the only CDK4/6 inhibitor to have demonstrated statistically significant overall survival benefit across three randomised controlled trials in metastatic breast cancer, and now meaningful survival data in the early setting as well, a distinction the company is pressing with prescribers and payers.
The NCCN Guidelines currently list Kisqali as a Category 1 preferred CDK4/6 inhibitor for both node-positive and high-risk node-negative early breast cancer, a designation that carries significant weight in US formulary negotiations and treatment algorithm positioning. Kisqali holds approvals in more than 100 countries, including a recent addition from China's National Medical Products Administration.
For Novartis, the maturing NATALEE dataset arrives at a commercially sensitive moment: ribociclib faces patent expiry pressure over the coming years, and demonstrating durable, deepening survival benefit in the broader early-stage population strengthens the case for sustained reimbursement and label expansions in markets where the adjuvant indication is still under review. Investors and oncologists will watch for whether the OS data influence guideline updates and payer coverage decisions in Europe, where several national health technology assessments are ongoing.