Phase III NATALEE Trial Results in Early Breast Cancer Patients


KISQALI has already set the standard for showing consistent benefit in a broad population of patients with stage II and III HR+/HER2- early breast cancer (EBC) at risk of recurrence, including those with no nodal involvement. According to the results presented at the ASCO 2023 Conference, at data cutoff January 11, 2023, KISQALI (ribociclib) plus endocrine therapy (ET), compared to ET alone, lowered the risk of cancer recurrence by 25.2% in stage II and III HR+/HER2- early breast cancer patients, along with a consistent, clinically meaningful invasive disease-free survival (iDFS) benefit across key pre-specified subgroups.

The table below shows KISQALI'S significant iDFS benefit extends across vital pre-specified subgroups in early breast cancer patients.


Hazard Ratio

95% CI

Intention-To-Treat Population


0.618, 0.906 (p=0.0014)

AJCC Tumor Stage II


0.525, 1.103

AJCC Tumor Stage III


0.592, 0.925

Node-positive disease


0.630, 0.944

Node-negative disease


0.341, 1.165

Pre-menopausal women and men


0.530, 0.983

Post-menopausal women


0.613, 0.997

Gripping in to more insights, KISQALI demonstrated consistent and promising results across secondary efficacy endpoints, including a 26% risk reduction in Distant Disease-Free Survival (DDFS) and a 28% risk reduction in Recurrence-Free Survival (RFS), indicating potential improvements in overall survival.

In terms of safety, KISQALI demonstrated a favorable safety profile at 400 mg, exhibiting a low incidence of symptomatic adverse events and a minimal requirement for dose adjustments during a three-year administration period. Additionally, the most frequently reported AEs of special interest (grade 3 or higher) were neutropenia (43.8%) and liver-related AEs (e.g., elevated transaminases) (8.3%). However, Grade 3 or higher QT interval prolongation and diarrhea were low for KISQALI at 1.0% and 0.6%, respectively. 

When compared to pooled data from the MONALEESA trials, which used a 600-mg dose of ribociclib for advanced breast cancer, the 400-mg starting dose demonstrated reduced rates of neutropenia. Thus, neutropenia occurred in 74% of cases, with 60% of events reaching grade 3 or higher severity. Apart from that, Novartis aims to submit this Phase III data to the US and European regulatory authorities by year's end. Lastly, these practice-changing results confirm KISQALI's distinctive and established profile as an effective treatment for HR+/HER2- metastatic breast cancer.


KOL insights

“These landmark results will fundamentally change how we treat patients with stage II and III HR+/HER2- early breast cancer who are in need of new, well-tolerated options that prevent their cancer from coming back.” –Expert Opinion

“Addressing this unmet need across such a broad patient population could help streamline treatment decisions for healthcare providers and keep many more at-risk patients cancer-free without disrupting their daily lives.” –Expert Opinion


After the announcement of the positive results, KISQALI became the first and only CDK4/6 inhibitor to demonstrate a consistent, clinically meaningful benefit across a broad population of patients with HR+/HER2- early breast cancer, regardless of disease stage, menopausal status, or nodal status. Catering to this extensive patient population in need has the potential to simplify treatment choices for healthcare professionals while ensuring that a larger number of vulnerable patients remain free from cancer, enabling them to maintain their normal routines without interruption. Altogether, the compelling findings of the NATALEE trial hold the promise of expanding CDK4/6 inhibitor treatment in the adjuvant setting, potentially doubling the beneficiary population.

Although the NATALEE trial delivered promising results across all participants, uncertainty arises for market expansion due to the mixed outcome in node-negative patients. Somehow, Novartis will have to face tough competition from Lilly's VERZENIO, requiring a struggle to gain market share and validate expansion into new patient categories.

Get a more detailed overview of the key developments in the domain at: HER2-Positive Early Breast Cancer Market, HER2-Positive Early Breast Cancer Epidemiology Forecast, HER2-Positive Early Breast Cancer Pipeline Insight