Novartis Kisqali® (ribociclib) in combination with endocrine therapy significantly extends overall survival compared with endocrine therapy alone in pre-/perimenopausal women with HR+/HER2- advanced breast cancer in MONALEESA-7 trial
Jun 04, 2019
Advanced breast cancer is an incurable disease - in the UK 85% of women with metastatic breast cancer will not survive for 5 years or more after diagnosis1
Ribociclib is the only CDK4/6 inhibitor to show significant overall survival data in women with advanced breast cancer2
This was observed in a Phase III, randomised, placebo-controlled trial of pre/peri-menopausal women in combination with endocrine treatment as initial therapy
MONALEESA-7 overall survival results will be presented as a late-breaker at the 2019 ASCO Annual Meeting and published in The New England Journal of Medicine
Camberley, UK, June 1, 2019– Novartis today announced statistically significant overall survival (OS) results for Kisqali (ribociclib) from its Phase III MONALEESA-7 trial.2 The trial studied the effects of ribociclib plus endocrine therapy (goserelin plus either an aromatase inhibitor or tamoxifen) as initial treatment compared to placebo plus endocrine therapy in pre- and perimenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.2 Ribociclib is not recommended to be used in combination with tamoxifen.
OS in the intent-to-treat population (n=672) met the early efficacy stopping criteria at a pre-specified interim analysis following 192 deaths, of which 83 (24.8%) and 109 (32.3%) had occurred in the ribociclib and placebo arms, respectively (median OS, not reached vs. 40.9 [95% CI: 37.8-NE] months; HR = 0.712; 95% CI: 0.535-0.948; p=0.00973). There was an approximate 29% relative reduction in the risk of death in the ribociclib arm shown in comparison to the placebo arm. No new safety signals were observed.2
“Despite a plethora of new developments in metastatic breast cancer in the last two decades, many of which have led to new therapies, only a few studies were able to demonstrate an improved overall survival. The MONALEESA-7 study has now achieved this for young women with advanced HR+/HER2- breast cancer, giving hope to a group of women often excluded from hormonal intervention studies,” said Dr Hartmut Kristeleit, Consultant Medical Oncologist in London.
“It is the first phase III study of a CDK4/6 inhibitor plus endocrine therapy to demonstrate a statistically significant improvement in overall survival as per study design to date.
In my opinion ribociclib is the new standard of care for pre- and peri-menopausal women with HR+/HER2- advanced breast cancer.”
Ribociclib is not recommended to be used in combination with tamoxifen but is approved for use in combination with an aromatase inhibitor and luteinising hormone-releasing hormone (LHRH) agonist in pre/peri-menopausal women with advanced, HR+/HER2- breast cancer. Therefore, the results from the pre-specified subgroup of patients who received an aromatase inhibitor as combination treatment are relevant to UK clinical practice.
In the subgroup of patients receiving an aromatase inhibitor (n=495), 61 deaths occurred in the ribociclib arm (24.6%) and 80 occurred in the placebo arm (32.4%). The median OS was not reached in the ribociclib arm and was 40.7 months in the placebo arm. There was a ~30% relative reduction in the risk of death in the ribociclib arm in comparison to the placebo arm (HR 0.699 [95% CI, 0.501 to 0.976]).2
Ribociclib combination therapy also showed significantly delayed time to chemotherapy (median not reached) compared with endocrine therapy alone (median 36.9 months); HR 0.596 (95% CI, 0.459-0.774).
Post-discontinuation treatment for both arms was well balanced (ribociclib vs. placebo arms included: chemotherapy [22.4% vs. 28.6%], hormonal therapy [22.4% vs. 20.4%] and CDK4/6 inhibitors [10.0% vs. 18.6%]. Antineoplastic therapies after discontinuation of study treatment were reported for 151 patients (68.9% of discontinued patients) in the ribociclib arm and 205 (73.2%) in the placebo arm.
Susanne Schaffert, Ph.D., CEO, Novartis Oncology, added, “Ribociclib is the only CDK4/6 inhibitor to achieve statistically significant overall survival in combination with endocrine therapy, and we are so proud to share these data with the medical and patient community. These exciting results add to the known efficacy and safety profile of ribociclib and solidify it as a standard of care for people living with HR+/HER2- metastatic breast cancer.”
In the UK, around 55,000 women are diagnosed with breast cancer each year.3 The most common form of breast cancer is hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-).4 It is the second most common cause of cancer death in UK women.5 Eighty five per cent of women diagnosed with advanced stage 4 or metastatic breast cancer will not live longer than five years.6
MONALEESA-7 is a global Phase III randomised, double-blind, placebo‑controlled study investigating the efficacy and safety of ribociclib plus endocrine therapy (an aromatase inhibitor or tamoxifen plus goserelin) versus placebo plus endocrine therapy as an initial treatment for premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer. A total of 672 eligible pre or perimenopausal women between the ages of 18 and 59 years were enrolled in the trial. The MONALEESA-7 OS results show that younger women with HR+/HER2- advanced breast cancer lived significantly longer with ribociclib plus endocrine therapy compared to women who received placebo plus endocrine therapy.3 Ribociclib is the only CDK4/6 inhibitor to demonstrate significantly longer overall survival in combination with endocrine therapy compared with endocrine therapy alone.78 9 10 11
About Kisqali® (ribociclib)
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 kinases 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide rapidly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.12
Kisqali in combination with endocrine therapy significantly extends overall survival compared to endocrine therapy alone for premenopausal women with HR+/HER2- advanced breast cancer.13 Overall survival follow-up is ongoing for the Phase III MONALEESA-2 and MONALEESA-3 trials, which are studying the effects of ribociclib in combination with endocrine therapy in postmenopausal women with HR+/HER2- advanced breast cancer.
In the UK Kisqali is indicated for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist. Kisqali is not recommended to be used in combination with tamoxifen.14
Kisqali can be taken with or without food as a once-daily oral dose of 600 mg (three 200 mg tablets) for three weeks, followed by one week off treatment. It is used in combination with an aromatase inhibitor or fulvestrant, which are used as hormonal anticancer therapies.14
When Kisqali is used in combination with an aromatase inhibitor, the aromatase inhibitor should be taken orally once daily continuously throughout the 28-day cycle. Please refer to the Summary of Product Characteristics (SmPC) of Kisqali and the aromatase inhibitor for additional details.14
When Kisqali is used in combination with fulvestrant, fulvestrant is administered intramuscularly on days 1, 15 and 29, and once monthly thereafter. Please refer to the SmPC of fulvestrant and Kisqali for additional details.14
In the ITT population (n=672) the most common all grade adverse events (that occurred in ≥20% of patients in either treatment arm) were: neutropenia, hot flush, nausea, leukopenia, arthralgia, fatigue, headache, anaemia and diarrhoea. The most common grade 3/4 (in ≥5% of patients in either treatment arm) were: neutropenia, leukopenia, and increased alanine aminotransferase. The median duration of exposure was 15.2 months (IQR 9.0- 19.8).15
In the subgroup of patients receiving an aromatase inhibitor (n=495) the most common all grade adverse events (that occurred in ≥20% of patients in either treatment arm) were: neutropenia, arthralgia, nausea, hot flush, leukopenia, fatigue, headache, alopecia, diarrhoea, anaemia, back pain, and vomiting. The most common grade 3/4 (in ≥5% of patients in either treatment arm) were: neutropenia and leukopenia. The median follow up was 19.2 months (IQR 16.2- 23.2).16
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).13
Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.13
About Novartis in Advanced Breast Cancer Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 130 000 people of nearly 150 nationalities work at Novartis around the world. Find out more at www.novartis.com.
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Hurvitz S, Seock-Ah I, Yen-Shen L et al. Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: Overall survival (OS) results. Presented at the 2019 ASCO Meeting, June 1, 2019,Abstract INSERT.