What Is Orserdu?
Orserdu is a commercial name for elacestrant, a medication developed to treat hormone receptor-positive, HER2-negative breast cancer. Orserdu is a selective estrogen receptor degrader (SERD), and it works by binding to the estrogen receptor (ER) and inducing its degradation, thereby blocking the action of estrogen in the cancer cells [citation; citation].
For What Is Used Orserdu?
Orserdu is indicated for treating postmenopausal women or adult men with ER-positive, HER2-negative, estrogen receptor one gene (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy [citation].
What Is Estrogen Receptor (ER)-Positive Breast Cancer?
The estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) are markers used in routine screening and detection of HR+ breast cancer [citation].
ER-positive breast cancer is a type of breast cancer fueled by the hormone estrogen.
In these breast cancers, estrogen can stimulate the cancer cells to grow. Hormone receptor-positive (HR+) breast cancer is the most common type, accounting for about two out of every three breast cancer cases in women [citation].
Treatment for hormone receptor-positive breast cancer often involves hormone therapy, which blocks the action of estrogen in the cancer cells. This can include medications that prevent estrogen production or block its action at the receptor or surgeries such as removing the ovaries, which are the primary source of estrogen in premenopausal women. Other treatments, such as chemotherapy or targeted therapies, may also be used [citation].
Currently, selective ER modulators (SERMs) and aromatase inhibitors (AIs) are the standard of care adjuvant systemic endocrine therapy for primary HR+ breast cancer [citation]. In contrast, the newer class of drugs are SERD's, among which is Orserdu, which induces ER degradation, unlike the older class of drugs that have the role of modulators [citation].
What Is HER2-Negative Breast Cancer?
HER2-negative breast cancer is a type of breast cancer that does not have an overabundance of the HER2 protein on its surface [citation]. The HER2 protein is a type of growth factor receptor on the surface of some breast cancer cells. Sometimes, the HER2 protein is overexpressed or amplified, meaning too many copies of the gene that codes for this protein. This can lead to an overproduction of the HER2 protein and drive the growth of cancer cells [citation].
What Is the Difference Between HER2-Positive and HER2-Negative Breast Cancer?
HER2-positive breast cancer is considered a subtype of breast cancer and is typically treated differently than HER2-negative breast cancer. HER2-positive breast cancer is often more aggressive and tends to grow and spread faster than HER2-negative breast cancer but is more likely to respond to the treatment [citation].
Overexpression of the HER2 gene is recorded in about 15% of breast cancer. A significant impact on cancer cell proliferation, migration, and survival characterizes it. However, with the identification of this specific protein during the 90s, the so-called "revolution" in the treatment of breast cancer succeeded because this protein is a characteristic target in treating patients [citation].
Triple-negative breast cancers comprise HER2-negative breast cancer patients, i.e., patients without the receptors usually found in this diagnosis. So they have neither estrogen or progesterone receptors. Unfortunately, molecular targeted therapy did not have a good outcome in HER2-negative cancer patients, so different strategies were developed. For example, PIK3 inhibitors have shown a good effect on the PIK3 pathway, which affects breast cancer development in this case. A similar evaluation applies to PARP inhibitors. However, developing angiogenesis inhibitors for HER2-negative breast cancer patients is a hot spot in research [citation].
Treatment for HER2-negative breast cancer may include surgery, radiation therapy, chemotherapy, hormone therapy, or a combination. In some cases, targeted therapies, such as medications that block the HER2 protein, may also be used. The specific treatment plan will depend on various factors, including the stage and grade of cancer, the age and overall health of the patient, and the patient's personal preferences [citation].
Who Developed Orserdu?
Orserdu is developed by Menarini [citation]. The Menarini Group is an Italian pharmaceutical company based in Florence, Tuscany, and it has three divisions:
Menarini Research
Menarini Biotech, and
Menarini Diagnostics.
It develops pharmacological solutions for cardiovascular diseases, oncology, pain/inflammation, asthma, and anti-infectives [citation].\
What Is the Mechanism of Action of Orserdu?
Orserdu is an estrogen receptor antagonist that binds to estrogen receptor-alpha (ERα). In ER-positive (ER+) HER2-negative (HER2-) breast cancer cells, elacestrant inhibits 17β-estradiol mediated cell proliferation at concentrations inducing degradation of ERα protein-mediated through the proteasomal pathway [citation].
Orserdu demonstrated in vitro and in vivo antitumor activity, including in ER+ HER2- breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors and those harboring ESR1 mutations [citation].
Estrogen receptors are proteins found in certain types of breast cancer cells that allow the cancer cells to grow in response to estrogen. Elacestrant works by binding to the estrogen receptors on the surface of cancer cells and causing the degradation of these receptors. This reduces the number of functional estrogen receptors in the cancer cells, inhibiting cell growth and division. By specifically targeting the estrogen receptors in cancer cells, elacestrant is designed to have a more targeted and effective impact on the cancer cells while minimizing the potential for side effects [citation]
In preclinical studies and clinical trials, elacestrant is effective in treating certain types of hormone receptor-positive (HR+) breast cancer, including HR+ breast cancer that has become resistant to other treatments. Elacestrant is thought to have the potential to be a useful treatment option for patients with HR+ breast cancer who have limited treatment options available to them [citation; citation].
What Are the Key Advantages of Orserdu?
Some of the critical advantages of elacestrant include:
Targeted treatment: By explicitly targeting the estrogen receptors in cancer cells, elacestrant is designed to have a more targeted and effective impact on the cancer cells while minimizing the potential for side effects.
Potential for increased efficacy: In preclinical studies and clinical trials, elacestrant is effective in treating certain types of hormone receptor-positive (HR+) breast cancer, including HR+ breast cancer that has become resistant to other treatments.
Fewer side effects: By targeting only the cancer cells, elacestrant is designed to have fewer side effects than other treatments that impact the entire body.
Potential for use in hormone receptor-positive (HR+) breast cancer: Elacestrant is specifically designed to treat HR+ breast cancer, which is fueled by estrogen [citation; citation].
What Are the Key Warnings and Precautions of Orserdu?
Orserdu (Elacestrant) is generally well-tolerated, but like all medications, it can cause side effects in some patients. Some of the most commonly reported side effects of elacestrant include:
Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking Orserdu at an incidence of 30% and 27%, respectively.
Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, Orserdu can cause fetal harm when administered to a pregnant woman. Administration of elacestrant to pregnant rats resulted in adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at maternal exposures below the recommended dose based on the area under the curve (AUC) [citation].
Additional Material
What Is Dyslipedimia?
Dyslipidemia is a medical condition characterized by abnormal levels of lipids (fats) in the blood, including high levels of cholesterol, triglycerides, or low levels of high-density lipoprotein (HDL) cholesterol. It is a significant risk factor for the development of cardiovascular disease and other health problems [citation].
What Is Hypercholesterolemia?
Hypercholesterolemia is a type of dyslipidemia characterized by abnormally high cholesterol levels in the blood. It is a significant risk factor for developing cardiovascular diseases, i.e., heart attacks and strokes. Genetic factors, unhealthy lifestyle choices, or other underlying medical conditions can cause hypercholesterolemia. Treatment may include lifestyle changes, such as diet, exercise, and medication to lower cholesterol levels [citation].
What Is Hypertriglyceridemia?
Hypertriglyceridemia is a type of dyslipidemia characterized by abnormally high levels of triglycerides, a type of fat, in the blood. Like hypercholesterolemia, it is a significant risk factor for cardiovascular disease, particularly if accompanied by low levels of high-density lipoprotein (HDL) cholesterol. Various factors, such as genetic conditions, obesity, uncontrolled diabetes, or certain medications, can cause hypertriglyceridemia. Treatment may include lifestyle changes, such as diet, exercise, and medication to lower triglyceride levels [citation].
Comments