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.”
“The Food and Drug Administration (FDA) has granted an expanded indication for the cyclin-dependent kinase 4/6 inhibitor palbociclib (Ibrance). The drug is now approved for use in combination with fulvestrant in women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer whose disease progressed following endocrine therapy.
“Palbociclib was initially approved in February 2015 for the treatment of estrogen receptor–positive, HER2-negative metastatic breast cancer, in women who had not yet received endocrine therapy. The new approval was granted under the FDA’s breakthrough therapy designation.
“The additional indication for palbociclib is based on results from the PALOMA-3 trial, which was stopped early in April 2015 after an interim analysis showed benefit in combination with fulvestrant when compared to fulvestrant and placebo.”
Two pharmaceutical giants are teaming up on a phase I/II clinical trial to see if their anti-melanoma drugs work better together than on their own. The drugs are GlaxoSmithKline’s Mekinist (trametinib), a U.S. Food and Drug Administration (FDA)-approved MEK inhibitor (a drug that targets MEK proteins), and Pfizer’s palbociclib, an experimental inhibitor of proteins called cyclin dependent kinases. These proteins make cells divide and are abnormally active in many cancers; the FDA has fast-tracked the review of using palbociclib to treat breast cancer. In addition, GlaxoSmithKline is already testing the combination of Mekinist with dabrafenib, the company’s experimental BRAF inhibitor.
American Association for Cancer Research │Oct 20, 2013
An experimental drug could keep melanomas and breast cancer from resisting targeted therapies, according to findings reported at the 2013 International Conference on Molecular Targets and Cancer Therapeutics. Called LEE011, the new drug inhibits proteins called cyclin-dependent kinases (CDKs), which make cells divide. The targeted CDKs are abnormally active in many cancers, including melanomas with BRAF mutations and breast cancers with PIK3CA mutations. The researchers found that LEE011 keeps cultured tumor cells from dividing and that combining the drug with targeted treatments prevents resistance in melanomas and breast cancer in mice. Now, these combination treatments are being tested in several phase I clinical trials on a variety of cancers in adults, as well as in children.
Among melanomas, BRAF-mutated disease gets the vast majority of attention. Fifty percent of melanomas harbor BRAF mutations, which can be targeted with BRAF inhibitors. However, despite its notoriety, BRAF is not the only important melanoma mutation.
Another melanoma-linked mutation can be found in the NRAS gene. Like BRAF mutations, NRAS mutations are ‘driver mutations’—a tumor with an NRAS mutation is dependent on the mutation for its growth and survival. Continue reading…
A study in The Lancet shows that the drug ipilimumab could treat melanomas that have spread to the brain, particularly in people who do yet not have neurological symptoms. Of 51 such patients treated with ipilimumab, 12 had tumors in the brain that shrank or did not get worse and 14 had tumors outside the brain that shrank or did not get worse. Ipilimumab (Yervoy) is an immune system booster that the FDA has approved for treating advanced melanomas.
An experimental drug could help control some melanomas that have BRAF or NRAS mutations, according to a report at an American Society of Clinical Oncology meeting. Tumors shrank or did not get worse in 8 out of 35 patients with the most common BRAF mutation (V600E), and in 6 out of 28 patients with NRAS mutations. This is the first targeted treatment for melanomas that have NRAS mutations. BRAF and NRAS mutations can activate a protein called MEK that is involved in cell division. The experimental drug, which is called MEK162, is a MEK inhibitor. The side effects of MEK162, which included diarrhea, rashes and swelling, were manageable.