Sacituzumab govetecan also known as IMMU-132 has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with triple-negative breast cancer (TNBC).
Triple-Negative Breast Cancer includes about 15% of all breast cancer types and has an annual incidence estimated to be about 40,000 people, with 20,000 diagnosed with metastatic TNBC, in the United States alone. As the name implies, Triple-Negative Breast Cancer does not express estrogen, progesterone or the HER2 receptor, and is, therefore, insensitive to most of the available targeted therapies for breast cancer treatment, including HER2-directed therapy.
TNBC has a particularly aggressive course and currently there is no single standard chemotherapy to treat patients with relapsed/refractory metastatic TNBC. New treatment strategies are needed.
Researchers recently reported the results of an early-phase clinical trial to evaluate the safety and effectiveness of treatment with the antibody drug conjugate sacituzumab govetecan (IMMU-132) in heavily pretreated individuals with advanced TNBC. Sacituzumab govitecan targets Trop-2, a calcium signal transducer that drives cancer cell growth in a majority of TNBC patients. IMMU-132 delivers high doses of SN-38, the active metabolite of Irinotecan that is 1000 times more active than Irinotecan itself.
In this early study IMMU-132 was well tolerated and produced an overall response rate of 30% in patients that had failed an average of 5 previous therapies. Additionally, 45% of patients had stable disease (SD), with 16% of the responses lasting for greater than 6 months.
IMMU – 132 Antibody-Drug Conjugate Improves Responses In Metastatic Triple-Negative Breast Cancer
Treatment with IMMU-132 (sacituzumab govitecan) elicited an overall response rate of 34 percent in patients with heavily pretreated metastatic triple-negative breast cancer (TNBC), according to updated findings from a clinical trial recently presented at the 2017 San Antonio Breast Cancer Symposium.1
About Triple-negative Breast Cancer
Approximately 12% of breast cancers are TNBC’s meaning that they are estrogen-receptor negative (ER-), progesterone-receptor negative (PR-), and human epidermal growth factor receptor 2-negative (HER2-). This means that TNBC is not stimulated to grow from exposure to the female hormones estrogen or progesterone, nor through an overactive HER2 pathway.
Unfortunately, many available and effective treatment options for the majority of breast cancers block the growth stimulating effects of ER, PR and/or HER2; therefore, TNBC has limited therapeutic options. TNBC tends to be more aggressive and grow at a rapid rate.
There are no modifiable risk factors for TNBC. These cancers tend to occur more frequently in young premenopausal women, in African-American women, and in women who carry the abnormal inherited breast cancer susceptibility gene BRCA1. Novel treatment options for TNBC have lagged behind that of other types of breast cancers and are definitely needed.2
About IMMU – 132
Sacituzumab govetecan (IMMU-132) is an antibody drug that targets Trop-2, a calcium signal transducer that drives cancer cell growth in a majority of TNBC patients. IMMU-132 delivers high doses of SN-38, the active metabolite of the chemotherapy drug Irinotecan that is 1000 times more active than Irinotecan itself. IMMU-132 has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with TNBC.3
The current study included 110 patients with TNBC that had failed two or more prior treatment regimens. IMMU-132 was administered on days one and eight of each 28-day cycle. Study patients received a median of 14.5 doses of the medication and the median duration of treatment was 4.9 months.
In addition to producing an overall response rate of 34% another 11% of patients had stable disease (SD) for 6 months or more resulting in an overall disease control rate of 45% Average overall survival was 12.7 months. The most common side effects were neutropenia, nausea, diarrhea, anemia, fatigue and vomiting. Those receiving prior checkpoint inhibitors had an overall response rate of 47% and responses were similar between those receiving treatment as a third-line therapy or beyond.
These results compare favorably to traditional response rates with other single-agent chemotherapy medications used beyond the first-line setting, which rang from 6% to 15% percent across clinical trials.
Connect with other patients on CancerConnect to discuss these and other results and experiences with TNBC.
Sacituzumab Govitecan Receives Breakthrough Designation for Triple-Negative Breast Cancer
The United States Food and Drug Administration (FDA) has designated the investigative agent, sacituzumab govitecan (IMMU-132), breakthrough designation for the treatment of triple-negative breast cancer.
The new FDA designation is for treatment of patients with advanced triple-negative breast cancer (TNBC) whose disease has progressed following 2 prior therapies.
According to Immunomedics Inc.’s press release announcing the update, breakthrough designation was developed by the FDA “to expedite the development and review of a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.”
Approximately 10-20% of breast cancers are referred to as triple-negative breast cancer (TNBC). These types of cancers are both hormone-negative and HER2-negative.
Hormone-negative breast cancer refers to a type of breast cancer that is both estrogen- and progesterone-receptor negative. This means that this type of cancer is not stimulated to grow from exposure to the female hormones estrogen and/or progesterone. Only about one-third or fewer breast cancers are hormone-negative.
Approximately 25-30% of breast cancers are referred to as human epidermal growth factor receptor (HER)2-positive, in which the cancer cells have a gene mutation that causes extra HER2 receptors to be present on the cell surface. Since the HER2 pathway is involved in cellular growth and replication, excessive HER2 receptors result in uncontrolled replication and spread of the HER2-positive cancer cells.
HER2-negative breast cancer refers to cancer that does not have a mutated HER2 pathway, and therefore, is not stimulated to replicate and spread through the activity of excessive HER2 receptors.
Many treatments are available specifically for hormone-positive breast cancers, as well as HER2-breast cancers. Since these treatments are ineffective in TNBC, research efforts are underway to find new treatment options or optimal combinations of agents for this type of breast cancer.
Standard treatment for TNBC typically consists of surgery, chemotherapy and/or radiation therapy. However, optimal chemotherapy regimens for TNBC continue to be explored.
IMMU-132 is referred to as an antibody-conjugate, and is still in investigate stages. It is comprised of an antibody that attaches to specific receptors called Trop-2 receptors. The antibody is attached to a drug that kills cancer cells, called SN-38.
Trop-2 receptors are often found in large numbers on the surface of cancer cells, but not healthy cells. Once IMMU-132 binds to the Trop-2 receptors, it delivers SN-38 into the cancer cell. This kills the cancer cell, while only affecting a small portion of healthy cells.
By targeting Trop-2 receptors, larger amounts of chemotherapy can be delivered to the cancer cells because healthy cells are largely spared from the cancer-killing effects of the treatment.
A recent clinical trial was conducted to further evaluate the effectiveness of IMMU-132 in patients with TNBC. The trial included patients with TMBC that had spread to distant sites in their body, and had received a median of 5 prior therapies. Final results from the trial are awaited to fully determine patient outcomes. Meanwhile, patient enrollment for continuing larger comparative trials with IMMU-132 in TNBC is ongoing.
IMMU-132 is also being evaluated in the treatment of other types of cancers in clinical trials.
A BRCA Gene Mutation in the Family Does Not Increase Cancer Risk for Those Without the Mutation
For women who do not have a BRCA1 or BRCA2 gene mutation, having a close relative with one of these mutations does not increase breast cancer risk. These results were published in the Journal of Clinical Oncology.
Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.
Women who test negative for a BRCA gene mutation—but who have family members with a mutation—are generally thought to have a risk of breast cancer that’s similar to that of women in the general population. A study published in 2007, however, raised concerns that relatives of BRCA mutation carriers may have a substantially increased risk of breast cancer even if they test negative for their family’s mutation.
To further explore cancer risk among close relatives of people with BRCA mutations, researchers conducted a study among more than 3,000 families with at least one case of breast cancer; 160 families had a BRCA1 mutation and 132 families had a BRCA2 mutation.
For women without a BRCA mutation, breast cancer risk was similar whether or not the woman’s family had a BRCA mutation. These results suggest that coming from a family with a BRCA1 or BRCA2 gene mutation does not increase cancer risk for those who test negative for the mutation.
Although this is reassuring news, women who test negative for their family’s gene mutation should continue to follow cancer screening guidelines. These women do not have the very elevated cancer risk that their affected relatives have, but they can still get cancer.
- Bardia et. al; GS1-07. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate, as ≥3rd-line therapeutic option for patients with relapsed/refractory metastatic triple-negative breast cancer (mTNBC): Presented at: 20167San Antonio Breast Cancer.
- Bardia A, Diamond JR, Mayer IA, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate (ADC) for the treatment of relapsed/refractory, metastatic triple-negative breast cancer (mTNBC): Updated results. Presented at: 2016 San Antonio Breast Cancer.
Bardia A, Diamond JR, Mayer IA, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate (ADC) for the treatment of relapsed/refractory, metastatic triple-negative breast cancer (mTNBC): Updated results. Presented at: 2016 San Antonio Breast Cancer
Immunomedics, Inc. Press Release. [U.S. Food and Drug Adminstration (FDA) Grants Breakthrough Therapy Designation to Immunomedics for Sacituzumab Govitecan for the Treatment of Patients with Triple-Negative Breast Cancer.](http://news.cancerconnect.com/sacituzumab-govitecan-receives-breakthrough-designation-for-triple-negative-breast-cancer/U.S.%20Food%20and%20Drug%20Adminstration%20(FDA%29%20Grants%20Breakthrough%20Therapy%20Designation%20to%20Immunomedics%20for%20Sacituzumab%20Govitecan%20for%20the%20Treatment%20of%20Patients%20with%20Triple-Negative%20Breast%20Cancer.) . Available at: . Accessed February 8, 2016.
 Smith A, Moran A, Boyd MC et al. Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening. Journal of Medical Genetics. 2007;44:10-15.
 Kurian AW, Gong GD, John EM et al. Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: findings from the Breast Cancer Family Study. Journal of Clinical Oncology. Early online publication October 31, 2011.
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