Verzenio (abemaciclib) in combination with fulvestrant significantly extended life by a median of 9.4 months in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer previously treated with endocrine therapy.
Lives were extended by a 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. Eli Lilly and Company sponsors Verzenio.
Results from the phase III MONARCH 2 clinical trial, which included both pre/peri- and postmenopausal women, were consistent across subgroups. Researchers presented the results, simultaneously published in JAMA Oncology, Sept. 29 at ESMO.
In patients previously treated with endocrine therapy whose cancer quickly returned or spread to other parts of the body, or primary endocrine resistance, the results were consistent with the intent-to-treat 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).
Both of these analyses were pre-defined and results are consistent with ITT results from the MONARCH 2 study that had previously demonstrated a statistically significant improvement in the primary endpoint of progression-free survival, with overall survival as a secondary endpoint.
In addition to extending life, an exploratory analysis of these data has shown Verzenio in combination with fulvestrant delayed 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, patients 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.
“While CDK4 and 6 inhibitors have changed the way oncologists treat HR+, HER2- advanced breast cancer in the past few years, we are just beginning to understand which of these therapies meet the enormously important goal of significantly extending life in patients with advanced breast cancer,” Professor of medicine and breast oncology in the division of hematology/oncology at the University of Vermont Cancer Center, and MONARCH 2 study investigator Peter A. Kaufman, said in a statement.
“These important new findings from MONARCH 2 demonstrate further the benefits of Verzenio, and arm oncologists with additional information as they aim to optimize treatment for patients, including those whose cancer progressed following endocrine therapy,” Kaufman said in a statement.
The safety profile was consistent with primary analysis of MONARCH 2. No new safety signals were observed with long term follow-up (median of 47.7 months). At the time of analysis, 17% of patients in the Verzenio arm continued treatment versus 4% in the placebo arm.
These positive results demonstrated 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.
Lilly said it plans to submit overall survival data to global regulatory authorities. Verzenio in combination with fulvestrant is approved in more than 50 countries worldwide.
Additional data for investigational use of Verzenio presented at ESMO include positive results from the monarcHER trial, the first randomized clinical trial of a CDK4 & 6 inhibitor in combination with 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.
