Verzenio™ (abemaciclib) Significantly Extends Life by a Median of 9.4 Months for Women with HR+, HER2- Advanced Breast Cancer in MONARCH 2 Study

Toronto, Oct. 09, 2019 (GLOBE NEWSWIRE) — Eli Lilly and Company (NYSE: LLY) announced that Verzenio (abemaciclib) in combination with fulvestrant significantly extended life by a median of 9.4 months in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (mBC) previously treated with endocrine therapy (median of 46.7 months vs median of 37.3 months with placebo plus fulvestrant; HR: 0.757; 95% CI: 0.606, 0.945; P = 0.0137). Results from the Phase 3 MONARCH 2 clinical trial, which included both pre/peri- and postmenopausal women, were consistent across subgroups. These results were presented as a late-breaking abstract in the Presidential Symposium, at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain and simultaneously published in JAMA Oncology.On April 5, 2019, Health Canada issued a Notice of Compliance (NOC) for Verzenio. In Canada, Verzenio is indicated for the treatment of estrogen and/or progesterone HR+and HER2-mBC: in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy; in combination with fulvestrant for women with disease progression following endocrine therapy; and as a single agent for women with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.“Canadian women living with metastatic breast cancer want therapies that effectively treat breast cancer, giving them more time with loved ones and the best quality of life”, says Cathy Ammendolea, Chair of the Board of Directors for the Canadian Breast Cancer Network (CBCN). “Having more treatment options for women living with advanced breast cancer means we continue to move in a direction that may enable these women to live their lives to the fullest.”Additionally, in women previously treated with endocrine therapy whose cancer quickly returned or spread to other parts of the body, called primary endocrine resistance, the results were consistent with the intent-to-treat (ITT) population (HR: 0.686; 95% CI: 0.451, 1.043). Similar results were observed in women whose cancer spread to their organs, such as liver or lungs (also known as visceral disease; HR: 0.675; 95% CI: 0.511, 0.891). These are characteristics of aggressive disease that indicate a woman may be more likely to do worse.Both of these analyses were pre-defined and results are consistent with the intent-to-treat (ITT) results from the MONARCH 2 study which had previously demonstrated a statistically significant improvement in the primary endpoint of progression-free survival, with overall survival as a secondary endpoint of the trial.In addition to extending life, an exploratory analysis of these data has shown Verzenio in combination with fulvestrant delayed the time to chemotherapy, with a median time to chemotherapy of 50.2 months versus 22.1 months in the placebo arm (HR: 0.625; 95% CI: 0.501, 0.779). In this exploratory analysis, women who died before receiving chemotherapy were included up until the date of death. This finding may be an important treatment consideration in advanced breast cancer as physicians aim to postpone the use of chemotherapy for as long as possible.“When treating patients with HR+, HER2- advanced breast cancer, as oncologists our aim is to effectively treat patients without compromising their quality of life and also improve their overall survival,” said Dr. Karen Gelmon, Medical Oncologist at BC Cancer Agency and Professor of Medicine at the University of British Columbia in Vancouver. “Results from MONARCH 2 are significant, further demonstrating that treatment with Verzenio may halt advanced breast cancer from progressing and subsequently extend life for patients.”The safety profile was consistent with that of the primary analysis of MONARCH 2. No new safety signals were observed with long term follow-up (median of 47.7 months) and at the time of analysis, 17 per cent of patients in the Verzenio arm remained on treatment versus 4 per cent in placebo arm.These positive results definitively showed that Verzenio plus fulvestrant reached statistical significance at a pre-planned interim analysis. Lilly will continue to monitor patients enrolled in the trial. Any additional analyses will be considered post-hoc (conducted after the current analysis). Lilly plans to submit these overall survival data to global regulatory authorities. Verzenio in combination with fulvestrant is currently approved in more than 50 countries worldwide, including Canada.Additional data for investigational use of Verzenio presented at ESMO include positive results from the monarcHER trial, the first randomized clinical study of a CDK4 & 6 inhibitor in combination with an endocrine therapy versus standard of care chemotherapy for HR+, HER2+ patients, and positive results from MONARCH plus, the first trial of a CDK4 & 6 inhibitor in a predominantly Chinese population of women with HR+, HER2- advanced breast cancer.About MONARCH 2MONARCH 2 is a Phase 3, randomized, double-blind, placebo-controlled trial that enrolled 669 patients with HR+, HER2- advanced or metastatic breast cancer who progressed on endocrine therapy. Patients were randomized 2:1 to Verzenio plus fulvestrant or placebo plus fulvestrant. Verzenio was dosed on a continuous dosing schedule until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Key secondary endpoints were objective response rate (ORR), overall survival (OS), and duration of response (DoR). Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for advanced disease. Patients could not have received chemotherapy or more than one line of endocrine therapy for advanced breast cancer.In the primary analysis of MONARCH 2, the most frequent adverse events (AEs) of any grade in the abemaciclib plus fulvestrant arm were diarrhea, neutropenia, nausea, and fatigue. Of these, the reported Grade 3 AEs (abemaciclib vs. placebo arm) were diarrhea (13.4% vs. 0.4%), neutropenia (23.6% vs. 1.3%), nausea (2.7% vs. 0.9%), and fatigue (2.7% vs. 0.4%). No patients in either arm experienced Grade 4 diarrhea, nausea or fatigue, and Grade 4 neutropenia was observed in 2.9 percent versus 0.4 percent of patients in the abemaciclib versus placebo arms, respectively.About mBCMetastatic breast cancer (mBC), also referred to as advanced breast cancer, is breast cancer that has spread beyond the breast to other areas in the body, most commonly the bones, lungs liver or brain1. Although metastatic cancers present themselves in different areas of the body, the disease still has the same type of cells shown in the original cancer and is still breast cancer2.The tumour’s HR and HER2 status determine sub-types of mBC3. The most common type is HR+ and HER2-, which occurs in about 70 per cent of breast cancer cases4. Despite improvements made with early detection and treatment, there is currently no cure for mBC. The five-year relative survival rate is 22 per cent for women with advanced breast cancer or mBC in Canada5.About Verzenio (abemaciclib)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.The full Canadian VERZENIO Product Monograph is available here.About Eli Lilly Canada Inc.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. Across the globe, 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 Eli Lilly Canada, please visit us at www.lilly.ca.VERZENIOTM registered trademark owned by Eli Lilly and Company; used under license. -30-1What is Metastatic Breast Cancer? (n.d.). Retrieved from https://cbcn.ca/en/what_is_mbc2What is metastatic cancer? – Canadian Cancer Society. (n.d.). Retrieved from http://www.cancer.ca/en/cancer-information/cancer-type/metastatic-cancer/metastatic-cancer/?region=nu3Metastatic Breast Cancer: Know Your Type. (n.d.). Retrieved from https://cbcn.ca/web/default/files/public/Living Legacy_Postcard_HR HER2-_Final_ENG.pdf4Canadian Partnership Against Cancer. Breast Cancer Control in Canada: A System Performance Special Focus Report. September 20125Canadian Cancer Society. www.cancer.ca . [Online] 2012. http://www.cancer.ca/en/cancer-information/cancer-type/breast/prognosis-and-survival/survival-statistics/?region=nu.Helen Stone
Eli Lilly Canada
stone_helen@lilly.com

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