Worldwide, breast cancer is the most frequently diagnosed cancer and the leading cause of death in women, accounting for 25% (1.67 million) of the total new cancer cases and 522,000 deaths per year (14% of total cancer deaths) in 2012 (http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx). For women in the United States, breast cancer is the most prevalent cancer and the second most common cause of cancer death, after lung cancer, with 40,290 deaths estimated in 2015 (15% of all cancer deaths). Annual incidence of breast cancer in the U.S. was expected to be approximately 234,190 in 2015.
About 10-20% of breast cancers do not have the receptors for the hormones, estrogen and progesterone, or for the human epidermal growth factor (HER2). As such, they are known as triple-negative breast cancer, or TNBC. This type of breast cancer tends to occur more frequently in younger women, in African-American women, and in women who have BRCA1 mutations. In addition, it is often more aggressive and spreads more quickly than other types of breast cancer.
Standard hormonal therapies for breast cancers or drugs that target the HER2 receptor are ineffective against TNBC since the cancer lacks the necessary receptors. Chemotherapy and radiation therapy remain the standard for TNBC therapy. Although TNBC typically responded well to initial treatments, the cancer has high recurrence, metastatic, and mortality rates.
TNBC is one of the solid cancers included in the Phase 2 study of the antibody-drug conjugate, sacituzumab govitecan (IMMU-132). For more information on this clinical trial, please refer to Clinical Trial.
Lung cancer is a malignant transformation of the lung tissue and is the deadliest form of cancer, claiming more lives than colorectal, prostate and breast cancers combined. Every year, lung cancer kills ~1.6 million people worldwide and ~160,000 people in the U.S, accounting for about 27% of all cancer deaths. In 2015, 221,200 new cases of lung cancer were expected in the U.S. Many of the symptoms of lung cancer (bone pain, fever, weight loss) are nonspecific and in the elderly, may be attributed to co-morbid illnesses. Furthermore, approximately 10% of the people with lung cancer do not demonstrate any symptoms at the time of diagnosis and in many patients, the cancer has already spread beyond the original site by the time they seek medical attention. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer.
There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope - non-small-cell lung cancer or NSCLC (85%) and small-cell lung cancer or SCLC (roughly 15%). The latter of which is the more aggressive form. SCLC often starts in the bronchi near the center of the chest and spreads quickly to other parts of the body. Cigarette smoking is the biggest risk factor for SCLC.
Because the disease has often spread throughout the body by the time SCLC is diagnosed, standard treatments for patients with SCLC are chemotherapy and radiation therapy. Survival statistics vary depending on the stage of the cancer when it is diagnosed. According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (http://www.cancer.org/cancer/lungcancer-smallcell/detailedguide/small-cell-lung-cancer-survival-rates), 5-year survival rates by stage for patients with small cell lung cancer between 1988 and 2001 were 31%, 19%, 8% and 2% for stage I to IV, respectively.
There are 3 main subtypes of NSCLC, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Patients with advanced-stage NSCLC usually are treated with chemotherapy, target drugs, or some combination of the two, while recently an checkpoint-inhibitor immunotherapy gained rapid approval for the squamous cell type based on a 15% objective tumor response and a median progression-free survival of 6 months.
Sacituzumab govitecan (IMMU-132) is currently in a Phase 2 clinical trial in patients with solid cancers, including lung cancer Clinical Trial.
Pancreatic cancer is often called a silent disease because it is difficult to detect and symptoms do not usually appear until the cancer has grown and often spread beyond the pancreas for quite some time. When symptoms do appear, they can be confused with other diseases. Depending on the stage and location of the cancer, surgery, chemotherapy and/or radiation therapy are used to treat this disease, but if the cancer has spread beyond the pancreas, therapy often is palliative, or focused on patient comfort.
According to the National Cancer Institute , an estimated 40,560 Americans died from pancreatic cancer in 2015, about 7% of all cancer deaths, making the disease the fourth leading cause of cancer death in the United States. About 48,960 new cases in both sexes were expected in 2015.
The cause of pancreatic cancer is not known, but a small percentage of people develop the disease as a result of a genetic predisposition, which gives them a higher risk of developing this disease. Smoking is also considered to be a risk factor. There are typically no symptoms at the early stage, nor is there yet a reliable screening test for early detection. Pain is often felt in the upper abdomen and sometimes, the back, as one of the earliest symptoms and it is exacerbated after meals or when lying down. Other symptoms include loss of appetite, weight loss, nausea, and general fatigue. If the common bile duct is blocked by the tumor, jaundice appears.
Treatment options depend on stage and location of the cancer, age, and general health of the patient. Potentially curative surgeries are performed when the cancer has started in the head of the pancreas (near the bile duct), which can allow earlier detection when bile duct blockage produces jaundice. Palliative surgery is a type of surgery chosen when the tumor is too widespread and is done to relieve the symptoms or complications caused by the cancer. If the cancer has not spread beyond the pancreas, therapy can be successful, but it is rare to find pancreatic cancer in the early stages. In later stages, various forms of chemotherapy or combinations of radiation and chemotherapy are given to try to control the disease, and ultimately therapy strives to reduce pain. For all stages combined, the overall 5-year relative survival for 2003-2009 was 6.0%. For patients with advanced cancers, the median survival is 4.5 months.
Sacituzumab govitecan (IMMU-132) is currently in a Phase 2 clinical trial in patients with solid cancers, including pancreatic cancer Clinical Trial.
Colorectal cancer is cancer that starts in either the colon or the rectum. Most cases of colorectal cancer are adenocarcinomas that begin as benign polyps from glands in the lining of the colon and rectum, which slowly develop into cancer. There is no single cause of colon cancer although the risk increases with age, a high fat diet, ulcerative colitis or Crohn’s disease, and a family or personal history of colorectal cancer.
Colorectal cancer remains a leading cause of cancer incidence and mortality worldwide. It is the third most commonly diagnosed cancer in men and the second in women, with over 1.2 million new cases and 608,700 deaths estimated to have occurred in 2008. In the U.S., with estimated 132,700 new cases and 49,700 deaths attributed to colorectal cancer in 2015 (http://www.cancer.gov/cancertopics/types/colon-and-rectal), the disease ranked 4th by incidence following lung, breast and prostate cancers in both sexes, and second only to lung cancer in mortality.
Over the past 10 years, there have been important strides that have reduced the mortality of this disease primarily through more widespread screening that can catch the disease early before extensive spread. Treatment depends partly on the stage of the cancer and may include surgery, chemotherapy, radiation therapy and targeted therapy. However, progress, while real, has been modest. When the disease is diagnosed early and the cancer is confined to its primary site, the 5-year relative survival rate reaches 90%. The rate decreases to 70% when the cancer has spread to regional lymph nodes and 12% when it has metastasized. For all stages combined, the 5-year relative survival rate is 64%.
Our antibody-drug conjugate, labetuzumab govitecan (IMMU-130), is in a Phase 2 study in patients with metastatic colorectal cancer. Information on this clinical trial can be obtained from Clinical Trial.