“The addition of the CDK4/6 inhibitor abemaciclib to fulvestrant significantly improved progression-free survival (PFS) and time to subsequent chemotherapy in pre- and perimenopausal women with hormone receptor–positive/HER2-negative advanced breast cancer, according to results from an analysis of the phase III MONARCH-2 trial (abstract 1002) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.”
“Mutations in HER2 were found to confer resistance to hormone therapy in some estrogen receptor (ER)-positive metastatic breast cancer cases, and resistance could be reversed by dual treatment with the hormone therapy fulvestrant (Faslodex) and the HER2 kinase inhibitor neratinib (Nerlynx), according to data presented during a media preview for the 2018 American Association for Cancer Research (AACR) Annual Meeting, to be held April 14–18 in Chicago.”
“The FDA approved abemaciclib for the treatment of women with hormone receptor-positive HER-2-negative advanced or metastatic breast cancer who progressed following endocrine therapy.
“The agency approved abemaciclib (Verzenio, Eli Lilly) — an investigational cyclin-dependent kinase 4/6 inhibitor —in combination with fulvestrant (Faslodex, AstraZeneca) following progression on endocrine therapy, and as a monotherapy for patients with metastatic disease previously treated with endocrine therapy and chemotherapy.”
“Previously the drug was approved as second-line monotherapy for women failing anti-estrogen therapy, and as second-line combination therapy with palbociclib (Ibrance). It was first approved by the FDA in 2002.”
“Eli Lilly and Company (NYSE: LLY) today announced that results from the Phase 3 MONARCH 2 study showed that abemaciclib, a cyclin-dependent kinase (CDK)4 & 6 inhibitor, in combination with fulvestrant, significantly improved progression-free survival (PFS) compared to treatment with fulvestrant alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy (median PFS, 16.4 vs. 9.3 months, respectively, HR: 0.553; 95% CI: 0.449, 0.681, P < .0000001). The data were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #1000) and simultaneously published online in the Journal of Clinical Oncology.”
“Adding abemaciclib to letrozole or anastrozole improved progression-free survival (PFS) compared with either aromatase inhibitor alone in women with HR+/HER2-negative breast cancer enrolled in the phase III MONARCH 3 study, according to Eli Lilly and Company, the manufacturer of the CDK4/6 inhibitor.
“MONARCH 3 (NCT02246621) is the second phase III trial of abemaciclib to demonstrate improved PFS in patients with HR+/HER2-negative breast cancer. In March, Lilly announced that in the MONARCH 2 study, combining abemaciclib with fulvestrant extended PFS compared with fulvestrant alone in patients who had progressed during or within 1 year of receiving endocrine therapy in the neoadjuvant or adjuvant setting, or during frontline endocrine treatment for metastatic disease.”
“Eli Lilly and Co’s combination of its experimental breast cancer drug and another widely used treatment slowed disease progression in patients who relapsed or did not benefit enough when treated with the anti-estrogen therapy.
“In August, an independent data monitoring committee recommended the late-stage study continue without modification, even though interim evaluation suggested the combination treatment was not delaying cancer progression.
“Lilly’s drug, abemaciclib, is part of the same new class of breast cancer treatments as Pfizer Inc’s Ibrance, and Novartis AG’s newly approved Kisqali.”
“Fulvestrant prolonged PFS compared with anastrozole among women with hormone receptor– positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy, according to a phase 3, randomized, double blind trial published in The Lancet.
” ‘The primary endpoint of this phase 3 study was met, with patients receiving fulvestrant having a significantly longer PFS than patients receiving anastrozole,’ John F.R. Robertson, MD, a professor at University of Nottingham Medical School and Royal Derby Hospital Centre in Derby, United Kingdom, and colleagues wrote. ‘This represents a meaningful and relevant finding for which clinical data are limited.’ ”
Doctors prescribe drugs known as CDK inhibitors to treat some women with estrogen-receptor-positive (ER+) metastatic breast cancer. Research into these drugs is ongoing, and new, promising CDK inhibitor options are on the horizon. Here, I address the current outlook for CDK inhibitors in ER+ breast cancer.
First, some background: ER+ breast cancers comprise about 70% of all breast cancers. The name reflects the fact that cells of these cancers express estrogen receptors (ERs), which are protein features targeted by many treatment strategies for this cancer type. The estrogen receptor (ER) protein is a treatment target not only because “it is there,” but mainly because it drives tumor cell proliferation in ER+ breast cancer. The activity of the ER depends on its binding to the hormone estrogen, and treatments known as endocrine drugs aim to prevent this interaction. Some endocrine drugs inhibit the synthesis of estrogen in the body (e.g., aromatase inhibitors, such as letrozole and anastrozole), and others prevent the interaction of estrogen with ERs (e.g., ER modulators such as tamoxifen, or the pure anti-estrogen drug fulvestrant). The problem of course is that, in metastatic breast cancer, resistance develops to each and every endocrine drug used. Continue reading…