Kisqali attempts reimb in early breast cancer

Company applies for reimbursement expansion…expected to be reviewed by the Cancer Disease Review Committee in the first half of the year

Unmet medical need persists… additional CDK4/6 inhibitor options needed

Following Verzenio's failed attempt to expand coverage for early-stage breast cancer, Kisqali has now stepped forward to tackle the same challenge.

According to Dailypharm coverage, Novartis Korea submitted an application last September to expand coverage for Kisqali (ribociclib), a CDK4/6 inhibitor, as adjuvant therapy in patients with high-risk Stage II and Stage III HR+ (hormone receptor positive)/ HER2- (human epidermal growth factor receptor 2 negative) early breast cancer. The company submitted the application last September and is awaiting its application to be reviewed by the Health Insurance Review and Assessment Service's Cancer Disease Review Committee later this year.

With Verzenio (abemaciclib), which shares the same CDK4/6 inhibition mechanism, having failed to clear the Cancer Disease Review Committee hurdle, attention is now focused on whether Kisqali can achieve a different outcome.

In the early breast cancer setting, Verzenio struggled from its first attempt. After a six-month wait following its application submission, the drug was first reviewed by the Cancer Disease Review Committee in May 2023, but reimbursement criteria were not established. Lilly resubmitted the application 5 months later in October, and the drug was reviewed again in March and July of last year—only to meet the same outcome.

This suggests that Kisqali’s reimbursement journey may also be challenging. In particular, the lack of overall survival (OS) data, which proved to be a major stumbling block for Verzenio, remains a key issue. In early-stage cancer, generating OS data is inherently difficult.

While Kisqali is expected to improve OS, direct data is not available yet. Invasive disease-free survival (iDFS) is used as a clinically meaningful surrogate endpoint with a strong correlation to OS in early breast cancer due to the disease characteristics. Kisqali demonstrated encouraging results in the NATALEE study.

Study results showed that for the primary endpoint, iDFS at 4 years was 88.5% for the Kisqali combination therapy group and 83.6% for the endocrine therapy alone group, representing an absolute improvement of 4.9 percentage points. The risk of invasive disease progression or death was reduced by 28.5% in the Kisqali group compared to the endocrine therapy alone group.

Furthermore, according to the 5-year NATALEE data presented at ESMO 2025, the Kisqali combination therapy reduced the risk of invasive disease progression or death by 28.4% compared to endocrine therapy alone. The 5-year iDFS was 85.5% in the Kisqali combination group and 81.0% in the endocrine therapy alone group, demonstrating a clinically meaningful 4.5% improvement.

Meanwhile, treatment for early-stage breast cancer patients involves local therapies such as surgery or radiation therapy, along with systemic adjuvant therapies like chemotherapy and endocrine therapy. Endocrine therapy-based treatment is the standard therapy for HR+/HER2- early-stage breast cancer.

In the early 2000s, aromatase inhibitor monotherapy or tamoxifen, combined with ovarian function suppression therapy for premenopausal patients, was recommended for HR+/HER2- early breast cancer patients. The goal of adjuvant therapy is to eliminate micrometastases, reduce the risk of recurrence, and prolong patient survival.

For high-risk early-stage breast cancer patients (stages II-III) with a high risk of recurrence, the risk of recurrence continues to rise over time even after completing standard endocrine therapy following surgery, presenting limitations in improving long-term prognosis. Reported recurrence rates range from 6–22% within five years and 22–52% over 20 years, highlighting a persistent unmet medical need.