Novartis Kisqali delivers consistently superior overall survival - MONALEESA-3 trial demonstrates more life for postmenopausal HR+/HER2- advanced breast cancer patients

  • In MONALEESA-3, Kisqali plus fulvestrant achieved statistically significant overall survival benefit vs. fulvestrant alone in postmenopausal women (HR=0.724; p=0.00455)
  • Kisqali is the only CDK4/6 inhibitor to demonstrate positive overall survival in two pivotal Phase III trials - consistently demonstrating approximately 30% reduction in the risk of death
  • Overall survival benefit proven with multiple combination partners and the largest number of patients in MONALEESA-3 plus MONALEESA-7 make Kisqali the CDK4/6 inhibitor with unparalleled overall survival evidence
  • MONALEESA-3 data to be presented in ESMO Congress 2019 Presidential Symposium

Basel, September 29, 2019 - Novartis today announced results from the MONALEESA-3 trial, which showed Kisqali (ribociclib) achieved statistically significant improvement in overall survival (OS). This is the second Phase III trial in which Kisqali combination therapy met the secondary endpoint of overall survival at the pre-planned interim analysis. MONALEESA-3 evaluated efficacy and safety of Kisqali plus fulvestrant in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. These data will be presented as a late-breaker oral presentation in the Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2019.

"Seen now in two Phase III trials, ribociclib consistently and significantly prolongs life among premenopausal and postmenopausal women, and in combination with an aromatase inhibitor and fulvestrant. These results arm oncologists with more evidence to make a confident treatment choice for their hormone receptor-positive metastatic breast cancer patients," said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center.

Kisqali in combination with fulvestrant met its secondary endpoint of overall survival, demonstrating a statistically significant improvement in survival with a 28% reduction in risk of death (median OS not reached vs. 40.0 months; HR=0.724; 95% CI: 0.568-0.924; p=0.00455). The significant extension in survival met the early efficacy stopping criteria at a pre-specified interim analysis. At 42 months, estimated rates of survival were 58% for Kisqali combination treatment and 46% for fulvestrant alone. Results in the first-line and second-line subgroups, including in patients who relapsed within 12 months of adjuvant treatment, were consistent with the overall MONALEESA-3 patient population.

Median PFS in the first-line was also reached at this analysis and demonstrated that Kisqali in combination with fulvestrant has a median PFS of 33.6 months compared to 19.2 months in the placebo arm (HR=0.546; 95% CI: 0.415-0.718). Additionally, the need for chemotherapy was delayed in all patients who were prescribed Kisqali plus fulvestrant (HR=0.696; 95% CI: 0.551-0.879).

"The remarkable results from MONALEESA-3 and MONALEESA-7 make Kisqali the CDK4/6 inhibitor with consistently superior overall survival," said Susanne Schaffert, PhD, President, Novartis Oncology. "In nearly 25 years, the five-year survival rates in HR+ metastatic breast cancer have improved by less than 5%. We are committed to helping give these women more life and are reimagining a world where metastatic breast cancer becomes a curable disease."

MONALEESA-3 is the largest trial to evaluate a CDK4/6 inhibitor plus fulvestrant as initial therapy in postmenopausal women (N=726). The trial included women with no prior endocrine therapy, including those diagnosed de novo, women who relapsed within 12 months of adjuvant therapy and women who progressed on endocrine therapy for advanced disease. The most common grade 3/4 adverse events of special interest observed in this analysis in patients who received Kisqali plus fulvestrant compared to fulvestrant alone were neutropenia (57.1% vs 0.8%), hepatobiliary toxicity (13.7% vs 5.8%), QTc prolongation (3.1% vs 1.2%), respiratory disorders (2.3% vs 3.3%) and interstitial lung disease (0.2% vs 0%).

"Pre-clinical data show that Kisqali is distinct from other CDK4/6 inhibitors in its ability to more selectively target and inhibit CDK4," said Jeff Engelman, MD, PhD Global Head of Oncology Research, Novartis Institutes for BioMedical Research. "CDK4 is a major driver of breast cancer progression and inhibiting it has been shown to block the growth of breast cancer cells."

There currently remains no cure for advanced breast cancer. Breast cancer is the number one cause of cancer death in European women, claiming the lives of more than 150,000 women in 2018.

About Kisqali (ribociclib)
Kisqali (ribociclib) is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone. Kisqali is the only CDK4/6 inhibitor to achieve statistically significant overall survival in two Phase III trials with two distinct patient populations. Overall survival results from MONALEESA-7 were presented at ASCO 2019, demonstrating Kisqali plus endocrine therapy significantly extends life in premenopausal women with HR+/HER2- advanced breast cancer. Overall survival follow-up is ongoing for the Phase III MONALEESA-2 trial.

Kisqali is approved for use in more than 75 countries around the world, including the United States and European Union member states. Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali in combination with an aromatase inhibitor was approved for the treatment of pre-, perior postmenopausal women as initial endocrine based therapy, and also indicated for use in combination with fulvestrant as both firstor second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide.

Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO) .

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

Important Safety Information FROM THE Kisqali EU SmPC
Kisqali (ribociclib) is a prescription medicine approved  in combination with an aromatase inhibitor as initial endocrine - based therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer or fulvestrant as initial endocrine - based therapy or following disease progression on endocrine therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if Kisqali is safe and effective in children or adolescents. Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Kisqali is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali can harm an unborn baby. Females who are able to become pregnant and who take Kisqali should use highly effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid grapefruit or grapefruit juice while taking Kisqali. The most common side effects (incidence >=20%) include infections, white blood cell count decreases, headache, cough, nausea, tiredness, diarrhea, vomiting, constipation, hair loss and rash. The most common Grade 3/4 side effects (incidence >5%) were infections, low neutrophils, low leukocytes, low red blood cells, abnormal liver function tests, low lymphocytes, low phosphate levels and vomiting. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

Please see full Prescribing Information for Kisqali, available at