Lilly's Verzenio (abemaciclib): First and Only CDK4/6 Inhibitor to Significantly Extend Overall Survival in Combination with Fulvestrant for HR+/HER2- Advanced Breast Cancer

July 31, 2019 /BioValleyBIOON/ -- U.S. pharmaceutical giantEli Lilly(Eli Lilly) recently announced that the targeted anticancer drug Verzenio (abemaciclib) inBreast CancerThe Phase III MONARCH 2 study demonstrated a statistically significant improvement in overall survival (OS, a secondary endpoint). Based on these data, Verzenio is the first and only CDK4/6 inhibitor to achieve a statistically significant improvement in OS when used in combination with fulvestrant.

The MONARCH 2 study was conducted in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer who had experienced disease progression on endocrine therapy, including premenopausal, perimenopausal, and postmenopausal patients, to evaluate the efficacy and safety of Verzenio in combination with fulvestrant.

Results from the pre-planned interim analysis demonstrated a statistically significant improvement in overall survival (OS) with Verzenio plus fulvestrant compared to placebo plus fulvestrant. Previously reported data showed a statistically significant improvement in progression-free survival (PFS, the primary endpoint) with Verzenio plus fulvestrant versus placebo plus fulvestrant (median PFS: 16.4 months vs. 9.3 months). Based on the PFS data, Verzenio has been approved in more than 50 countries worldwide. In this study, no new safety signals were observed in the current analysis, and the safety profile of Verzenio was consistent with its established safety profile.

Eli LillyThe plan is to submit these data to regulatory authorities and at the medical conference held later this year.MeetingPublish detailed data above.

Eli LillyTumorLilly President Anne White stated, “I believe we must continue to fight this devastating disease, as women with metastatic breast cancer are striving relentlessly to live more fulfilling lives. Although Verzenio has already demonstrated significant benefits in progression-free survival, we are pleased that Verzenio is the first and only CDK4/6 inhibitor that, in combination with fulvestrant, significantly extends overall survival in premenopausal/perimenopausal/postmenopausal patients.”

Eli LillyTumorMaura Dickler, M.D., Vice President of Late-Stage Development, stated, “HR+/HER2− metastatic breast cancer is a complex disease that remains incurable. The clear overall survival analysis from the MONARCH 2 study demonstrated a significant improvement in overall survival among women with this type of breast cancer. For many physicians and patients, overall survival is the most important endpoint. Historically, it has been difficult to achieve meaningful improvements in this endpoint for women with advanced breast cancer, including those whose disease progressed after endocrine therapy.”

The active pharmaceutical ingredient of Verzenios is abemaciclib, 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, 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 overactivity is highly frequent, as CDK4/6 are key downstream targets of ER signaling. Preclinical data indicate that dual inhibition of CDK4/6 and ER signaling has synergistic effects and can inhibit the growth of G1-phase ER+ breast cancer cells. Clinical evidence also demonstrates that abemaciclib crosses the blood-brain barrier. In patients with advanced cancer, including those with breast cancer, the concentrations of abemaciclib and its active metabolites (M2 and M20) in the cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio was approved in the United States in October 2017FDAApproved for the treatment of patients with HR+/HER2- advanced or metastatic breast cancer. This drug is indicated for: (1) combination with an aromatase inhibitor (AI) as initial endocrine therapy in postmenopausal women; (2) combination with fulvestrant in women whose disease has progressed on endocrine therapy; (3) monotherapy in adult patients with metastatic disease that has progressed despite prior control with endocrine therapy and chemotherapy.

The approval of Verzenio was based on data from two Phase III clinical studies (MONARCH 2 and MONARCH 3). In the MONARCH 2 study, the Verzenio plus fulvestrant treatment group demonstrated a significantly prolonged progression-free survival (PFS) compared to the fulvestrant plus placebo group (median PFS: 16.4 months vs. 9.3 months). The MONARCH 3 study evaluated Verzenio in combination with an aromatase inhibitor (AI) as initial endocrine therapy for postmenopausal women with HR+/HER2- advanced breast cancer who had not previously received systemic therapy for advanced disease. The data showed that the Verzenio plus AI treatment group had a significantly prolonged PFS compared to the placebo plus AI group (median PFS: 28.2 months vs. 14.8 months).

Currently, three CDK4/6 inhibitors have been marketed, in addition toEli LillyIn addition to Verzenio, there arePfizerIbrance (palbociclib) andNovartisKisqali (ribociclib). (Bioon.com)

Original Source:Lilly's Verzenio® (abemaciclib) Significantly Extended Life in Women with HR+, HER2- Advanced Breast Cancer in MONARCH 2