Verzenio® Significantly Reduced the Risk of Cancer Recurrence by 25 per cent for People with HR+, HER2- High Risk Early Breast Cancer

Verzenio in combination with endocrine therapy is the only CDK4 & 6 inhibitor to demonstrate a statistically significant improvement in invasive disease-free survival (IDFS) in early breast cancer

The Phase 3 monarchE trial evaluating the effects of two years of Verzenio treatment added to endocrine therapy achieved the primary endpoint of IDFS, demonstrating definitive and clinically meaningful results among people whose breast cancer is at a high risk of recurrence

Data presented in the Presidential Symposium at the European Society for Medical Oncology (ESMO) 2020 Virtual Congress and simultaneously published in the Journal of Clinical Oncology (JCO)

TORONTO, Sept. 24, 2020 /CNW/ - Eli Lilly and Company (NYSE: LLY) announced Verzenio^® (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) significantly decreased the risk of breast cancer recurrence by 25 per cent compared to standard adjuvant ET alone for people with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high risk early breast cancer (HR: 0.747; 95% CI: 0.598, 0.932; p = 0.0096). This statistically significant benefit was consistent across all pre-specified subgroups and corresponds to a 3.5 per cent difference between arms (92.2 per cent in the Verzenio arm and 88.7 per cent in the control arm) at two years. These results are from a preplanned interim analysis with 323 IDFS events observed in the intent-to-treat population across both arms, including 136 in the Verzenio arm and 187 in the control arm. The data were presented on September 20, 2020 in the Presidential Symposium at the European Society for Medical Oncology (ESMO) 2020 Virtual Congress and simultaneously published in the Journal of Clinical Oncology.

Safety data from monarchE were consistent with the known safety profile of Verzenio and no new safety signals were observed. At the time of analysis, approximately 70 per cent of patients in each arm were still on the two-year treatment period. The median follow up was approximately 15.5 months in both arms. The median duration on Verzenio was 14 months.

"When we are treating patients with high risk early stage breast cancer our goal is to decrease the risk of the cancer recurring and cure more patients," said Dr. Karen Gelmon, Medical Oncologist at BC Cancer Agency and Professor of Medicine at the University of British Columbia in Vancouver. "Results from monarchE are significant, as this study reports that Verzenio led to a statistically significant reduction in the risk of cancer recurrence suggesting it is an effective and well tolerated treatment for these patients."

monarchE randomized 5,637 patients with HR+, HER2- high risk early breast cancer from more than 600 sites in 38 countries, including 9 study sites in Canada. High risk was defined by cancer that spread to the lymph nodes, a large tumor size, or high cellular proliferation (as determined by tumor grade or Ki-67 index). Patients were treated for two years (treatment period) or until they met criteria for discontinuation. After the treatment period, all patients will continue ET for five to 10 years, as clinically indicated.

"Canadian women living with high risk early breast cancer want therapies that effectively treat breast cancer and reduce the risk of their cancer recurring," says Cathy Ammendolea, Chair of the Board of Directors for the Canadian Breast Cancer Network (CBCN). "Given that approximately 30 per cent of women living with high risk early breast cancer have a recurrence, having more treatment options means we continue to move in a direction toward enabling these women to live their lives to the fullest."

The addition of Verzenio to endocrine therapy also resulted in an improvement in distant relapse-free survival, or the time to developing cancer that has spread to other parts of the body. The combination reduced the risk of developing metastatic disease by 28 per cent (HR: 0.717; 95% CI: 0.559, 0.920), with the largest reductions occurring in rates of metastases to the liver and bone. This treatment benefit was consistent across all prespecified subgroups. Two-year distant relapse-free survival rates were 93.6 per cent in the Verzenio arm and 90.3 per cent in the control arm.

Overall survival results were immature and monarchE will continue through the completion date, estimated to be June 2027. At the time of the interim analysis, the IDFS results are considered definitive. All patients on monarchE will be followed until primary analysis and beyond to assess overall survival and other endpoints. Lilly will submit the monarchE data to regulatory authorities.

About the monarchE Study
monarchE is a Phase 3, multicenter, randomized, open-label trial that enrolled 5,637 patients with HR+, HER2- node-positive, high risk early breast cancer. Patients were randomized 1:1 to Verzenio (150 mg twice daily) plus standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone. Patients were treated for two years (treatment period) or until they met criteria for discontinuation. After the treatment period, all patients will continue on endocrine therapy for five to 10 years, as clinically indicated. The primary objective is invasive disease-free survival (IDFS) defined according to the Standard Definitions for Efficacy Endpoints (STEEP) criteria. In adjuvant breast cancer trials, this includes the length of time before any cancer comes back, a new cancer develops or death. Secondary objectives include distant relapse-free survival, overall survival, safety, pharmacokinetics and health outcomes. 

High risk was specifically defined as women (any menopausal status) and men with resected HR+, HER2- invasive early breast cancer with either ≥4 pathologically positive axillary lymph nodes (ALNs) or 1 to 3 positive ALNs and at least one of the following high-risk features: primary invasive tumor size ≥5 cm, histological grade 3 tumor, or central Ki-67 index ≥20%. If applicable, patients must have also completed adjuvant chemotherapy and radiotherapy prior to enrolling and have recovered from all acute side effects.

About Early Breast Cancer
Breast cancer is the most common cancer among women worldwide.ⁱ An estimated 90 per cent of all breast cancer is diagnosed at an early stage.ⁱⁱ Approximately 70 per cent of all breast cancers are HR+, HER2-, the most common subtype.ⁱⁱⁱ Even within this subtype, HR+, HER2- breast cancer is a complex disease, and many factors – such as if the cancer has spread to the lymph nodes and the biology of the tumor – can impact the risk of recurrence. Approximately 30 per cent of people diagnosed with HR+ early breast cancer will experience the return of their cancer, and potentially incurable metastatic disease.^iv

About Verzenio^®
Verzenio^® (abemaciclib) is an inhibitor of cyclin-dependent kinases (CDK)4 & 6, which are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.

In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio is Lilly's first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.

INDICATION
In Canada, Verzenio^® (abemaciclib) is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer:

• in combination with an aromatase inhibitor in postmenopausal women as initial endocrine based therapy.
• in combination with fulvestrant in women with disease progression following endocrine therapy. Pre- or perimenopausal women must also be treated with a gonadotropin-releasing hormone (GnRH) agonist.
• as a single agent in women with disease progression following endocrine therapy and at least 2 prior chemotherapy regimens. At least one chemotherapy regimen should have been administered in the metastatic setting, and at least one should have contained a taxane.

Clinical effectiveness of Verzenio in combination with an aromatase inhibitor is based on the benefit observed in patients treated with Verzenio in combination with letrozole or anastrozole for the treatment of postmenopausal women with advanced breast cancer.

About Eli Lilly Canada
Eli Lilly and Company is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by Colonel Eli Lilly, who was committed to creating high quality medicines that meet people's needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.

Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto, which eventually produced the world's first commercially-available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.

For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA

ⁱ World Health Organization. Breast cancer: prevention and control. https://www.who.int/cancer/detection/breastcancer/en/index1.html. Accessed: September 8, 2020.

ⁱⁱ Howlader N, et al. SEER Cancer Statistics Review, 1975-2013. http://seer.cancer.gov/csr/1975_2013/. Accessed: September 8, 2020.

ⁱⁱⁱ Howlader N, Altekruse S, Li C. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5).

^iv Reinert T and Barrios CH. Optimal Management of Hormone Receptor Positive Metastatic Breast Cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20.

SOURCE Eli Lilly Canada Inc.

Media Contact: Helen Stone, Lilly Canada, [email protected]; Alyssa Acorn, Cohn & Wolfe, [email protected] , [phone]