Novartis’ CDK4/6 Inhibitor Kisqali Demonstrates Significant Overall Survival Benefit as First-Line Therapy in HR+/HER2- Advanced Breast Cancer

June 10, 2019 /Bio ValleyBIOON/ -- Swiss pharmaceutical giantNovartis(Novartis) recently announced the evaluation of the targeted anticancer drug Kisqali (ribociclib) for treatmentBreast CancerThe pivotal Phase III MONALEESA-7 study demonstrated statistically significant overall survival (OS) data. Advanced breast cancer in premenopausal women is the leading cause of cancer-related death among women aged 20–59 years. Kisqali is the only CDK4/6 inhibitor to achieve a statistically significant OS benefit when combined with endocrine therapy in patients with advanced breast cancer. Results from this study further solidify Kisqali as the standard of care for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer.

This study was conducted in premenopausal and perimenopausal women with HR+/HER2- advanced or metastatic breast cancer to evaluate the efficacy and safety of Kisqali combined with endocrine therapy (goserelin plus an aromatase inhibitor or tamoxifen) as an initial treatment regimen compared to endocrine therapy alone.

Previously published data demonstrated that Kisqali combined with endocrine therapy (goserelin plus an aromatase inhibitor) doubled progression-free survival (PFS) compared to endocrine therapy alone (goserelin plus an aromatase inhibitor) (median PFS: 27.5 months vs. 13.8 months; HR=0.569, 95% CI: 0.433–0.74).

These OS data, from a prespecified interim analysis conducted after 192 death events, demonstrated that the significant prolongation of overall survival met the early efficacy stopping criteria (median OS: not reached vs. 40.9 months [95% CI: 37.8–NE]; HR=0.712 [0.535–0.948]; p=0.00973). At month 42, the overall survival rate in the intent-to-treat population (n=672) was 70.2% in the Kisqali combination therapy group versus 46.0% in the endocrine therapy group. At the data cutoff, 35% of patients in the Kisqali combination therapy group remained on treatment, and no new safety signals were observed. Kisqali is not indicated for use in combination with tamoxifen.

Subgroup analysis results showed that, compared with the use of an aromatase inhibitor alone, Kisqali in combination with an aromatase inhibitor reduced the risk of death by 30.0% (median OS: not reached vs. 40.7 months [37.4–NE]; HR=0.699 [0.501–0.976]), and Kisqali in combination with tamoxifen reduced the risk of death by 20.9% (HR=0.791 [0.454–1.377]). Kisqali is not indicated for use in combination with tamoxifen. In the primary analysis of the MONALEESA-7 study, patients receiving tamoxifen plus placebo had a mean increase in electrocardiogram QT interval (QTcF) of ≥10 milliseconds compared with those receiving an aromatase inhibitor plus placebo.

Dr. Sara Hurvitz, Medical Director of the Clinical Research Office at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, and Director of the Breast Cancer Clinical Trials Program, stated: “In cancer trials, overall survival benefit is considered the ‘gold standard,’ but this poses a challenge in HR+/HER2- metastatic breast cancer. The MONALEESA-7 study reached this important endpoint earlier than expected. Findings such as those for Kisqali are what we hope to see in everyClinical TrialThe achievements made have realized an improvement in overall survival in incurable diseases (such as metastatic breast cancer), which represents a genuine and significant progress for patients.”

It is estimated that globally, approximately 267,000 women are diagnosed with advanced breast cancer each year. Up to one-third of patients initially diagnosed with early-stage breast cancer will subsequently progress to advanced disease, for which there is currently no cure. In premenopausal women, advanced breast cancer is a biologically distinct and more aggressive disease, representing the leading cause of cancer-related mortality among women aged 20–59 years. These young patients face unique challenges, including premature menopause, emotional distress, and strain on their professional and personal lives.

Kisqali is an oral targeted CDK4/6 inhibitor that selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), restoring cell cycle control and blockingTumorCell Proliferation. Dysregulation of the cell cycle is a hallmark of cancer, and CDK4/6 are overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 are key regulators of the cell cycle, triggering the transition from the growth phase (G1 phase) to the DNA synthesis phase (S phase). In estrogen receptor-positive (ER+) breast cancer, CDK4/6 overactivity is highly prevalent, as CDK4/6 are key downstream targets of ER signaling. Preclinical data demonstrate that dual inhibition of CDK4/6 and ER signaling has a synergistic effect and can inhibit the growth of G1-phase ER+ breast cancer cells.

To date, Kisqali has been approved in more than 70 countries worldwide. The drug was initially approved in the United States and the European Union in March and August 2017, respectively, in combination with an aromatase inhibitor as initial endocrine therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer. In July and December 2018, the U.S. and EU approvals for Kisqali were expanded to include premenopausal, perimenopausal, and postmenopausal women in combination with an aromatase inhibitor as initial endocrine therapy, and it is also indicated in combination with fulvestrant as first- or second-line therapy for postmenopausal women. (Bioon.com)

Original Source:Novartis Kisqali significantly extends life in women with HR+/HER2- advanced breast cancer in MONALEESA-7 trial