Novartis Presents New Kisqali Data Demonstrating Consistent Overall Survival Benefit Across Genomic Subtypes in HR+/HER2- Metastatic Breast Cancer

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On December 8, Novartis presented new data on the CDK4/6 inhibitor Kisqali (ribociclib) at the 2021 San Antonio Breast Cancer Symposium (SABCS), showing that: similar to its effects in indolent and aggressive ET-resistant subtypes, Kisqali combined with endocrine therapy (ET) demonstrated consistent overall survival (OS) benefits across various genomically intrinsic subtypes of HR+/HER2- advanced or metastatic breast cancer (mBC).

An extensive exploratory analysis of nearly 1,000 tumor samples demonstrated that Kisqali + ET combination therapy consistently provided significant OS benefits across major intrinsic subtypes compared to ET treatment alone (Luminal A: n=542; HR=0.75; 95% CI: 0.58-0.96; p=0.021; Luminal B: n=278; HR=0.69; 95% CI: 0.50-0.95; p=0.023; HER2-enriched: n=147; HR=0.60; 95% CI: 0.40-0.92; p=0.018).

In HR+/HER2- breast cancer, HER2 overexpression subtype is associated with resistance to ET treatment and poor prognosis. In this subtype, Kisqali + ET combination therapy shows significant efficacy, with a median OS reaching 40.3 months, compared to 29.4 months for ET monotherapy. Among patients with the Luminal A subtype, Kisqali + ET combination therapy demonstrates the longest survival benefit, with a median OS of 68.0 months, compared to 54.6 months for ET monotherapy. In the basal-like subtype (which behaves more like triple-negative breast cancer [TNBC]), both Kisqali + ET combination therapy and ET monotherapy show poor OS outcomes, with median OS of 19.4 months and 21.2 months, respectively (n=30; HR=1.89; 95% CI: 0.80-4.47; p=0.148).

These data follow the biomarker analysis of the Monalesa trial, which was presented at SABCS 2020 and published in the Journal of Clinical Oncology. The analysis showed that Kisqali demonstrated a progression-free survival (PFS) benefit in the most common subtype of metastatic breast cancer.

The four intrinsic subtypes of breast cancer (Luminal A, Luminal B, HER2-overexpressed, and Basal-like) show significant differences in incidence, survival rates, and response to treatment. At this conference, the insights provided by genomic intrinsic subtypes complemented and expanded the information offered by standard clinical parameters and pathological markers. To date, Kisqali remains the only CDK4/6 inhibitor in the entire MONALEESA population that has demonstrated consistent overall survival (OS) benefits, regardless of metastatic sites and number of metastases, prior treatments, combination endocrine therapy, lines of previous therapy, or menopausal status.

CDK, or Cyclin-Dependent Kinase, is a key kinase involved in cell cycle regulation. CDK4/6 inhibitors can effectively block tumor cells from progressing from the G1 phase to the S phase, confining cell division to the G1 phase, thereby inhibiting the proliferation of cancer cells.

Kisqali is the second CDK4/6 inhibitor approved for marketing globally and has now been approved in more than 95 countries. In the United States and the European Union, Kisqali is approved for: (1) use in combination with an aromatase inhibitor as initial endocrine therapy for the treatment of HR+/HER2- locally advanced or metastatic breast cancer in premenopausal, perimenopausal, and postmenopausal women; (2) use in combination with fulvestrant as initial endocrine therapy or as a second-line treatment following disease progression on prior endocrine therapy for the treatment of HR+/HER2- advanced or metastatic breast cancer in postmenopausal women.

In October this year, the listing application for Kisqali (ribociclib) was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA).

Reference Source: New Kisqali® Data Shows Consistent Overall Survival Benefit Across Genomic and Clinical Subtypes of Interest in HR+/HER2- Metastatic Breast Cancer