Novartis Announces Positive Topline Results for Kisquali as AdjuvantTreatment for Early Breast Cancer

On March 27, 2023, Novartis reported topline results from the NATALEE trial, stating that Kisqali (ribociclib) plus endocrine therapy significantly reduced the risk of disease recurrence compared to standard endocrine therapy alone in patients with HR+/HER2- early breast cancer, including those patients with no nodal involvement.

NATALEE is a global, Phase 3, multicenter, randomized, open-label trial to evaluate the efficacy and safety of Kisqali as adjuvant treatment with endocrine therapy versus endocrine therapy alone in patients with stage 2 and 3 HR+/HER2- early breast cancer. The primary endpoint of NATALEE is invasive disease-free survival (iDFS), and secondary endpoints include safety, quality of life, and overall survival, among others. More than 5100 adult patients with HR+/HER2- breast cancer were randomized in the trial, including patients with tumor stages 2A, 2B, or 3, irrespective of nodal status. In the study, patients received a lower starting dose (400 mg) of Kisqali than the starting dose indicated for metastatic breast cancer (600 mg). Kisqali was administered for a duration of 36 months, whereas endocrine therapy was administered for a total of 60 months in both groups.

In October 2021, the FDA approved Eli Lilly’s Verzenio (abemaciclib) for the adjuvant treatment of adult patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%. The approval was based on data from the monarchE clinical trial. In the study, patients were randomized to receive either 2 years of Verzenio plus their physician’s choice of standard endocrine therapy or standard endocrine therapy alone. Verzenio is currently the only cyclin-dependent kinase (CDK) 4/6 inhibitor that has received this indication. Most recently, on March 3, 2023, the FDA updated the label for Verzenio and removed the Ki-67 requirement based on longer-term data.

If Kisqali receives FDA approval for adjuvant use in early-stage breast cancer without nodal involvement, this may place it at an advantage compared to Verzenio, which requires patients to have node-positive, early breast cancer at high risk of recurrence. In monarchE, Verzenio as adjuvant treatment with endocrine therapy reduced the risk of recurrence by 35%. Novartis has stated that results from NATALEE will be presented at an upcoming medical meeting. Many will be anticipating the detailed results from NATALEE to determine how Kisqali measures up to Verzenio.

The third FDA-approved CDK4/6 inhibitor, Pfizer’s Ibrance (palbociclib), did not show a reduction in risk of recurrence in women with HR+/HER2- early breast cancer in the PALLAS study that reported in May 2020, which compared Ibrance plus standard adjuvant endocrine therapy to standard adjuvant endocrine therapy alone.

For more details, please refer to the therapeutic class summary for Oncology: Breast Cancer, available on the IPD Platform. IPD Analytics will continue to update our coverage as new information becomes available.