“Novartis’ CDK4/6 inhibitor Kisqali has picked up Breakthrough status in the US as an initial endocrine-based treatment in certain patients with breast cancer.
“The US Food and Drug Administration has awarded the designation for of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.”
“Pfizer Inc. (NYSE:PFE) today announced updated progression-free survival (PFS) results from the Phase 3 PALOMA-2 trial reinforcing the clinical benefit of IBRANCE® (palbociclib) combined with letrozole. The data, which will be presented at the 2017 San Antonio Breast Cancer Symposium (SABCS) on December 8 [abstract #P5-21-03], demonstrate that the combination of IBRANCE plus letrozole reduced the risk of disease progression by 44 percent and improved median PFS by more than one year compared to letrozole plus placebo (27.6 months [95% CI: 22.4, 30.3] vs 14.5 months [95% CI: 12.3, 17.1]) when used as the initial treatment for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer (HR=0.56 [95% CI: 0.46, 0.69]). This updated, post-hoc analysis included a median follow-up of more than three years, which is the longest to date of any Phase 3 study of a CDK 4/6 inhibitor.”
“AstraZeneca’s Faslodex has been cleared on both sides of the Atlantic for use in combination with a CDK4/6 inhibitor.
“In the EU, the drug’s use has been approved for use alongside the CDK4/6 inhibitor palbociclib to treat a certain form of breast cancer, in the US it can be prescribed in combination with the CDK4/6 inhibitor abemaciclib.
“Both the European Commission and US Food and Drug Administration have approved the combination for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.”
“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.”
“About one in five patients with post-chemotherapy metastatic breast cancer attained an objective response to single-agent therapy with the cyclin-dependent kinase (CDK)4/6 inhibitor abemaciclib, results of a phase II trial showed.
“Responses were durable, lasting an average of almost 9 months, and more than 40% of patients obtained clinical benefit. Abemaciclib’s safety and tolerability were consistent with previous clinical experience, as no new or unexpected adverse events occurred among 132 patients who received the drug.”
“The FDA recently approved ribociclib (Kisqali) for use in combination with an aromatase inhibitor as initial therapy for treatment of postmenopausal women with HR+/HER2-negative advanced or metastatic breast cancer.
“Ribociclib, an inhibitor of CDK4/6, was approved based on data from the phase III MONALEESA-2 trial, which was ended early following the first preplanned interim analysis. In this analysis, the combination of ribociclib and the aromatase inhibitor letrozole met the trial’s primary endpoint by demonstrating statistically significant improvement in progression-free survival (PFS) compared to letrozole alone.”
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…
“G1 Therapeutics, Inc., a clinical-stage oncology company, announced today the expansion of its pipeline of novel cancer therapies with the initiation of three development programs in breast cancer. G1 is enrolling a Phase 2 study of its intravenous CDK4/6 inhibitor trilaciclib for the treatment of triple-negative breast cancer (TNBC), and a Phase 1b/2a study of its oral CDK4/6 inhibitor G1T38 for the treatment of estrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer. In addition, G1 is advancing G1T48, its oral selective estrogen receptor degrader (SERD) with the goal of commencing a Phase 1 trial in the fourth quarter of 2017.”
“A neoadjuvant regimen combining the CDK4/6 inhibitor abemaciclib with anastrozole induced a response rate of 54.7% in patients with HR+/HER2-negative early-stage breast cancer, according to findings from the phase II neoMONARCH trial presented at the 2016 San Antonio Breast Cancer Symposium.
“The study also met its primary endpoint of reduction in Ki67 expression level at week 2. The abemaciclib combination yielded a geometric mean change in Ki67 from baseline to day 15 of -92.6%.”