Verzenio is the first and only CDK4 & 6 inhibitor in combination with fulvestrant to achieve statistically significant improvement in overall survival
MONARCH 2 was a Phase 3 study including both pre/peri- and postmenopausal women whose cancer progressed following endocrine therapy
INDIANAPOLIS, IN, USA I July 30, 2019 I Eli Lilly and Company (NYSE: LLY) today announced that Verzenio (abemaciclib) demonstrated a statistically significant improvement in overall survival in the Phase 3 MONARCH 2 clinical trial. These results were from a pre-planned interim analysis and are definitive. MONARCH 2 evaluated Verzenio in combination with fulvestrant for the treatment of women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer previously treated with endocrine therapy. The study included both pre/peri- and postmenopausal women.
The analysis showed that treatment with Verzenio in combination with fulvestrant met its secondary endpoint of overall survival. The MONARCH 2 study previously demonstrated a statistically significant improvement in progression-free survival, the trial’s primary endpoint which served as the basis for its approval of this regimen in more than 50 countries around the world. No new safety signals were observed in this analysis of MONARCH 2, consistent with the established safety profile of Verzenio.
“I believe we must continue to fight this devastating disease because the women who are living with metastatic breast cancer want to do everything they can to lead more fulfilling lives and be there for those who need them most,” said Anne White, president, Lilly Oncology. “While Verzenio had already shown an impressive benefit for progression-free survival, we are delighted that Verzenio is the first and only CDK4 & 6 inhibitor in combination with fulvestrant that has significantly extended life for both pre/peri- and postmenopausal women.”
Lilly plans to submit these data to regulatory authorities and present the detailed data at an upcoming medical meeting later this year.
“This definitive overall survival analysis from MONARCH 2 showed significant improvement in overall survival for women living with HR+, HER2- metastatic breast cancer, a complex disease that remains incurable,” said Maura Dickler, M.D., vice president, late stage development, Lilly Oncology. “For many doctors and patients overall survival is the most important endpoint. It’s been difficult in the past to achieve meaningful improvements in this endpoint for women with advanced breast cancer, including those whose cancer progressed after prior endocrine therapy.”
About MONARCH 2
MONARCH 2 is a Phase 3, randomized, double-blind, placebo-controlled trial that enrolled 669 patients with HR+, HER2- 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 metastatic disease. Patients could not have received chemotherapy or more than one line of endocrine therapy for metastatic breast cancer.
About Advanced Breast Cancer
Breast cancer is the most common cancer in women worldwide, with more than 2 million new cases diagnosed in 2018.1 An estimated 268,600 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S. in 2019.2 Advanced breast cancer includes metastatic breast cancer, meaning cancer that has spread from the breast tissue to other parts of the body, and locally or regionally advanced breast cancer, meaning the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.3 Of all early stage breast cancer cases diagnosed in the U.S., approximately 30 percent will become metastatic4 and an estimated 6 to 10 percent of all new breast cancer cases are initially diagnosed as being metastatic.5 Survival is lower among women with a more advanced stage at diagnosis: five-year relative survival is 99 percent for localized disease, 85 percent for regional disease, and 27 percent for metastatic disease.6 Other factors, such as tumor size, also impact five-year survival estimates.6
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.
INDICATION
Verzenio is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer:
- 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
- as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting
About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly’s commitment to people with cancer, please visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real 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 those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom. P-LLY
© Lilly USA, LLC 2019. ALL RIGHTS RESERVED.
Verzenio ® is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.
Fulvestrant (Faslodex®), MedImmune/AstraZeneca. MedImmune Limited/AstraZeneca provided fulvestrant for the MONARCH 2 trial.
1 International Agency for Research on Cancer. Global Health Observatory. GLOBOCAN 2018. Geneva: World Health Organization; 2018. http://gco.iarc.fr/. Accessed July 25, 2019.
2 American Cancer Society. Cancer Facts & Figures 2019.
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed July 25, 2019.
3 American Cancer Society. Understanding Advanced Cancer, Metastatic Cancer and Bone Metastases. https://www.cancer.org/treatment/understanding-your-diagnosis/advanced-cancer/what-is.html. Accessed July 25, 2019.
4 O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005;10 Suppl 3:20-9. PMID: 16368868 DOI: 10.1634/theoncologist.10-90003-20.
5 Metastatic Breast Cancer Network. 13 Facts about Metastatic Breast Cancer. http://www.mbcn.org/13-facts-about-metastatic-breast-cancer/. Accessed July 25, 2019.
6 American Cancer Society. Breast Cancer Facts & Figures 2017-2018. Atlanta: American Cancer Society, Inc. 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf. Accessed July 25, 2019.
SOURCE: Eli Lilly
