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Novartis Drug Ribociclib (Kisqali®) Shows Significant Promise in Targeted Treatment of Young Women with Advanced HR+/HER2-Negative Breast Cancer, Who Are Also Treated with Standard-of-Care Endocrine Therapy, According to Announcement at ASCO 2019

On June 1, 2019, it was announced that the international, randomized phase III MONALEESA-7 clinical trial has found that adding the Novartis drug ribociclib (Kisqali®) to standard-of-care endocrine therapy significantly improved overall survival for pre-menopausal women with advanced hormone receptor (HR)-positive/HER2-negative breast cancer compared with endocrine therapy alone. After 42 months of follow-up, the survival rate was 70% for women who took the combination therapy compared with 46% for women who received endocrine therapy only. Advanced breast cancer is the leading cause of cancer death in women 20 to 59 years of age. The MONALEESA-7 study results were presented on June 1, 2019 at the American Society of Clinical Oncology (ASCO) Annual Meeting ( )in Chicago, Illinois, and were featured in a June 1 ASCO press briefing. The ASCO abstract (LBA 1008) is titled “Phase III MONALEESA-7 trial of Premenopausal Patients with HR+/HER2- Advanced Breast Cancer (ABC) Treated with Endocrine Therapy ± Ribociclib: Overall Survival (OS) Results.” “This is the first study to show improved survival for any targeted therapy when used with endocrine therapy as a first-line treatment for advanced breast cancer,” said the study’s lead author Sara A. Hurvitz (photo), MD, Director of the Breast Cancer Clinical Research Program at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, CA. “The use of ribociclib as a front-line therapy significantly prolonged overall survival, which is good news for women with this terrible disease. Overall survival benefit is considered the 'gold standard' in cancer trials, but is challenging to achieve in HR+/HER2- metastatic breast cancer. MONALEESA-7 reached this important endpoint earlier than anticipated. Impactful results like these ribociclib findings are what we wish for in every clinical trial, and to achieve overall survival improvement in an incurable disease, like metastatic breast cancer, is truly an outstanding advancement for patients."

“Advanced breast cancer in pre-menopausal women can be very aggressive. It is important and encouraging to see a targeted therapy that significantly increases survival for younger women with this disease,” said ASCO Expert Harold J. Burstein, MD, PhD, who was not involved in the trial. Dr. Burstein is a breast cancer oncologist at the Dana Farber Cancer Institute and Brigham & Women’s Hospital. He is also an Associate Professor of Medicine at Harvard Medical School.

M.J. DeCoteau, Executive Director of Rethink Breast Cancer, said, "Younger women living with advanced breast cancer encounter unique challenges as they face an incurable illness at the prime of their lives - they may be students, new moms or just embarking on their careers. Breast cancer is the leading cause of cancer death in women 20-59, so knowing an approved treatment has been proven to help them live longer is an outstanding advancement and provides new hope for women with this devastating disease."

Advanced breast cancer is less common in pre-menopausal women than in older women, but its incidence is increasing in the group of younger women. In the United States, in women ages 20 to 39, the incidence of advanced breast cancer increased 2% per year between 1978 and 2008.

Ribociclib is a therapy that inhibits the activity of cancer-cell promoting enzymes known as cyclin-dependent 4/6 kinases (CDK 4/6). In July 2018, the US Food and Drug Administration approved the expanded indication for ribociclib in combination with an aromatase inhibitor to include pre- and peri-menopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer.

"Kisqali has characteristics that make it distinct from other CDK4/6 inhibitors. For one, Kisqali shows especially strong inhibition against CDK4. In pre-clinical data, Kisqali is four- to five-fold more potent against CDK4 compared to CDK6. CDK4 is likely the dominant CDK in breast cancer and a pivotal driver of disease progression," said Jeff Engelman, MD, Global Head of Oncology Research, Novartis Institutes for BioMedical Research.

Susanne Schaffert, PhD, CEO, Novartis Oncology, added, "Kisqali is the only CDK4/6 inhibitor to achieve statistically significant overall survival benefit in combination with endocrine therapy, and we are so proud to share these powerful data with the medical and patient community. These exciting results add to the proven efficacy and safety profile of Kisqali, solidify it as a standard of care for people living with HR+/HER2- metastatic breast cancer. and inspire us to continue to reimagine medicine."

The MONALEESA-7 clinical trial is the first to focus exclusively on women under age 59 who were pre-menopausal and had advanced breast cancer for which they had not received prior endocrine therapy.

Investigators randomly assigned women to ribociclib (a tablet), or to a placebo tablet. All women also received goserelin, an injectable endocrine therapy that suppresses estrogen, and one of three other therapies: the nonsteroidal aromatase inhibitors letrozole (Femara) or anastrozole (Arimidex), which lower estrogen production, or tamoxifen, which has been used to treat breast cancer for over 40 years and blocks the effects of estrogen in breast tissue.

672 women were enrolled in the study. After a median follow-up of 34.6 months, 173 (26%) were still receiving the therapies, with 116 (35%) of the women still receiving ribociclib and 57 (17%) still receiving the placebo.


The women who received ribociclib lived a median of 23.8 months without the disease progressing compared with 13 months for women who received the placebo.

The researchers observed that after 42 months of follow-up, for patients receiving ribocilcib, the survival rate was 70% when given with endocrine therapy compared with 46% when given with placebo. Overall this represented a 29% relative reduction in the risk of death.

In addition, the survival rate of 71% and 70% for women who took ribociclib in combination with tamoxifen or a nonsteroidal aromatase inhibitor, respectively, compared with a survival rate of 55% and 43%, respectively, for women who received placebo in combination with tamoxifen or aromatase inhibitors only.


The researchers are now doing analyses of patient-reported outcomes as well as sub-analyses of the clinical findings, including looking at biomarkers and circulating tumor DNA that may help them determine which women might benefit most from ribociclib.
The investigators are studying the use of ribociclib in women and men with early-stage HR+, HER2-negative breast cancer in combination with endocrine therapy and other cancer indications.

This study received funding from Novartis, the manufacturer of the ribociclib drug.


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 targeted therapy, including CDK4/6 inhibitors, in combination with endocrine therapy, to demonstrate significantly longer overall survival compared to endocrine therapy alone as initial endocrine-based treatment for advanced breast cancer in the MONALEESA-7 trial. Overall survival follow-up is ongoing for the Phase III MONALEESA-2 and MONALEESA-3 trials.

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 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-, peri-, or post-menopausal women as initial endocrine-based therapy, and also indicated for use, in combination with fulvestrant, as both first- or second-line therapy in post-menopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide.

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

(Photo is from Yahoo News article--see link below. Photo is originally from AFP (Agence France-Presse), an international news agency headquartered in Paris, France.)

[ASCO press release] [Novartis press release] [UT MD Anderson Cancer Center press release]

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