Novartis Kisqali Reports Longest Median Overall Survival of 4.5 Years in Postmenopausal HR+/HER2- Metastatic Breast Cancer

June 03, 2021 /BioonBIOON/ --Novartis(Novartis) recently announced CDK4/6 inhibitor Kisqali (ribociclib)Breast cancerLatest overall survival (OS) results from the Phase III MONALEESA-3 trial. The study was conducted in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Following an additional 16.9 months of follow-up, an exploratory OS analysis evaluated Kisqali plus fulvestrant combination therapy versus fulvestrant monotherapy as first- or second-line treatment for postmenopausal women with HR+/HER2- metastatic breast cancer. The analysis revealed that,After more than 4 years of long-term follow-up, compared with fulvestrant, the clinically relevant overall survival (OS) benefit of Kisqali plus fulvestrant continued to exceed one year.。These latest OS data will be presented at the 2021 ASCO Annual Meeting.

The specific data are as follows:After a median follow-up of 56.3 months, the median OS in the fulvestrant monotherapy group was 41.5 months, while the median OS in the Kisqali + fulvestrant group reached 53.7 months (HR = 0.73; 95% CI: 0.59–0.90), representing the longest OS data reported to date for the treatment of postmenopausal women with HR+/HER2- metastatic breast cancer.

Additionally, compared with fulvestrant, Kisqali + fulvestrant extended OS in both the first-line treatment subgroup (median OS: not reached vs. 51.8 months; HR=0.64; 95% CI: 0.46-0.88) and the second-line treatment subgroup (median OS: 39.7 months vs. 33.7 months; HR=0.78; 95% CI: 0.59-1.04), reducing the relative risk of death by 36% and 22%, respectively.

Notably,In this study, a 36% reduction in the relative risk of death was observed in the first-line (1L) postmenopausal population, highlighting that Kisqali is the only CDK4/6 inhibitor to demonstrate an overall survival (OS) benefit when combined with fulvestrant as first-line therapy.

The results of this exploratory post hoc analysis are consistent with those previously reported at the 2019 European MedicalTumorThe overall survival (OS) analysis data presented at the European Society for Medical Oncology (ESMO) Congress and published in *The New England Journal of Medicine* (NEJM) demonstrated that, compared with the fulvestrant group, the OS results for the Kisqali plus fulvestrant group were statistically significant, with a 28% reduction in the risk of death (HR = 0.72; 95% CI: 0.568–0.924; p = 0.00455). The subgroup analysis results were consistent with the survival data in the intent-to-treat (ITT) population.

Time to chemotherapy was delayed by 4 years (48.1 months) in the Kisqali + fulvestrant group versus 28.8 months in the fulvestrant group (HR=0.70; 95% CI: 0.57–0.88).. Adverse events were consistent with the results of previously reported Phase 3 trials.

Dennis J. Slamon, Director of Clinical/Translational Research at the UCLA Jonsson Comprehensive Cancer Center, stated: "Successfully demonstrating an improvement in overall survival in incurable diseases such as metastatic breast cancer is a major achievement, and is also what we in mostClinical Trialthe ultimate goal pursued. When the MONALEESA-7 trial at SABCS 2020ConferenceWhen the median overall survival (OS) data of nearly 5 years was announced for premenopausal female patients, it was the first time we had seen a CDK4/6 inhibitor achieve such a long median OS in metastatic disease. Encouragingly, a median OS of nearly 4.5 years was observed in postmenopausal female patients in the MONALEESA-3 trial, underscoring that Kisqali offers patients the hope of prolonged survival while maintaining quality of life.”

NovartisTumorDr. Susanne Schaffert, President, stated: "As the OS data mature, we are proud that Kisqali continues to stand out, providing longer survival for both younger and older women with metastatic breast cancer. These data confirm the sustained efficacy of Kisqali across a broad population of patients with HR+/HER2- metastatic breast cancer, regardless of line of therapy. These findings are both unique and encouraging. Our work to explore the benefits of Kisqali continues, with ongoing evaluation of its potential in the adjuvant setting."

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 is overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 is a key regulator of the cell cycle, capable of 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 overactivation is highly prevalent, and CDK4/6 serves as a key downstream target of ER signaling. Preclinical data indicate that dual inhibition of CDK4/6 and ER signaling exerts a synergistic effect and can inhibit the growth of G1-phase ER+ breast cancer cells.

Kisqali was initially approved in the United States and the European Union in March and August 2017, respectively (based on results from the MONALEESA-2 study), in combination with an aromatase inhibitor as initial endocrine therapy for the treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer. In July and December 2018, respectively, Kisqali received expanded approvals in the US and EU for use in combination with an aromatase inhibitor as initial endocrine therapy in premenopausal, perimenopausal, or postmenopausal women, and also for use in combination with fulvestrant as first- or second-line therapy in postmenopausal women.

Kisqali is the largest-scale first-lineClinical TrialClinical evidence for the CDK4/6 inhibitor confirms consistent and sustained efficacy compared with endocrine therapy alone. Kisqali has demonstrated a statistically significant overall survival benefit in two distinct patient populations, including premenopausal and postmenopausal women with HR+/HER2- advanced breast cancer.

Currently,NovartisInvestigating the therapeutic potential of Kisqali in early breast cancer to continue reshaping the clinical treatment of breast cancer. The company is collaborating with the clinical cancer research organization——`Tumor`The phase III NATALEE clinical trial, conducted in collaboration with Translational Research In Oncology (TRIO), investigated Kisqali in combination with endocrine therapy as adjuvant treatment for patients with HR+/HER2- early breast cancer. (Bioon.com)

Original Source: Novartis Kisqali reports longest median overall survival in postmenopausal HR+/HER2- metastatic breast cancer patients