Kisqali Receives EU Approval as First-Line Treatment for HR+/HER2- Advanced, Metastatic Breast Cance

Novartis announced that the European Commission (EC) approved Kisqali (ribociclib) in combination with an aromatase inhibitor for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer as initial endocrine-based therapy. Kisqali is the first CDK4/6 inhibitor approved in Europe based on a first-line Phase III trial that met its primary endpoint of progression-free survival (PFS) at interim analysis.

"This approval of Kisqali reinforces our recognized leadership in cancer research and our commitment to innovative targeted therapies," said Bruno Strigini, CEO, Novartis Oncology. "We are proud of our collaboration with study investigators and patients, which provides the medical community with an important new treatment option for women with advanced or metastatic breast cancer."

EU approval follows a positive opinion granted in June by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), which was based on superior efficacy and demonstrated safety of Kisqali plus letrozole versus letrozole alone in the pivotal Phase III MONALEESA-2 trial. The opinion included a recommendation that allows oncologists the flexibility to prescribe Kisqali with any aromatase inhibitor (i.e., letrozole, anastrozole or exemestane) they deem most appropriate for their patient.

MONALEESA-2 enrolled 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy for their advanced breast cancer and showed that Kisqali plus letrozole, an aromatase inhibitor, reduced the risk of progression or death by 43% over letrozole alone (median PFS=25.3 months (95% CI: 23.0-30.3) vs. 16.0 months (95% CI: 13.4-18.2); HR=0.568 (95% CI: 0.457-0.704; p<0.0001)[1]. More than half of patients (55%) with measurable disease taking Kisqali plus letrozole experienced a tumor reduction of at least 30 percent.

Up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease, for which there is currently no cure. Globally approximately 250,000 women are diagnosed with advanced breast cancer each year.

Kisqali can be taken orally once-daily with or without food at a suggested starting dose of 600 mg (three 200 mg tablets) for three weeks, followed by one week off treatment. Kisqali is taken in combination with continuous use of any aromatase inhibitor.

This decision is applicable to all 28 European Union member states plus Iceland, Norway and Liechtenstein. 

Additional regulatory filings are underway with other health authorities worldwide.

In March 2017, the US Food and Drug Administration (FDA) approved Kisqali, in combination with any aromatase inhibitor, as a treatment for metastatic breast cancer. Ribociclib in combination with letrozole was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a category 1 option for HR+/HER2- postmenopausal metastatic breast cancer patients.

Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Novartis is continuing to assess Kisqali through the robust MONALEESA clinical trial program, which includes two additional Phase III trials, MONALEESA-3 and MONALEESA-7 that are evaluating Kisqali in combination with multiple endocrine therapy partners across a broad range of patients, including premenopausal women. MONALEESA-3 is evaluating Kisqali in combination with fulvestrant compared to fulvestrant alone in postmenopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. MONALEESA-7 is investigating Kisqali in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in premenopausal women with HR+/HER2- advanced breast cancer who have not previously received endocrine therapy. These trials are fully enrolled.

Novartis is initiating two multi-center, randomized, double-blind Phase III clinical trials, EarLEE-1 and EarLEE-2, to evaluate the safety and efficacy of Kisqali with endocrine therapy as adjuvant therapy in pre- and postmenopausal women who have not previously received treatment with CDK4/6 or aromatase inhibitors. EarLEE-1 aims to assess Kisqali with adjuvant endocrine therapy compared to adjuvant endocrine therapy alone in women with HR+/HER2- high-risk early breast cancer. EarLEE-2 will investigate Kisqali with adjuvant endocrine therapy compared to adjuvant endocrine therapy alone in women with HR+/HER2- intermediate-risk early breast cancer.

The CompLEEment-1 study is evaluating the safety and efficacy of Kisqali plus letrozole in men and pre- or postmenopausal women with HR+/HER2- advanced breast cancer with no prior hormonal therapy for advanced disease. The open-label, multicenter, Phase IIIb CompLEEment-1 trial is currently enrolling participants.