Immunoassay May Identify Early-Stage Pancreatic Cancer

An investigational immunoassay can accurately identify pancreatic cancer, potentially giving clinicians the ability to identify and treat the disease in its early stages, according to research presented at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium.

The assay uses a monoclonal antibody to hone in on malignant pancreatic cells; for added benefit, investigators are also employing the antibody to deliver targeted radiotherapy to tumor cells.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference.

The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said. The protein is not present in normal pancreatic tissue or in other types of malignancies. It also is rarely detected in pancreatitis, making it highly specific for pancreatic cancer.

In the small study, Dr. Gold and his associates evaluated 68 patients who had undergone surgery for pancreatic cancer. The investigators obtained information about disease stage from surgical notes about the spread of the disease. They also evaluated 19 healthy controls.

The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting all stages of pancreatic cancer.

“The PAM4 blood test is very specific for pancreatic cancer. If the assay is positive, there is a high positive diagnostic likelihood that the patient has pancreatic cancer,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

If validated, the assay would be valuable for the management of patients with the disease. Most patients do not have symptoms until the advanced stages of tumor growth, when cure is unlikely. Currently, only an estimated 5% of patients with pancreatic cancer survive to 5 years, according to the American Cancer Society.

The PAM4 antibody has the potential to be part of an effective therapy as well.

“Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” Dr. Gold explained.

Researchers have already begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy of the tumor cells in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

“By using the combination of early detection and therapy improvements, we hope to be able to come up with a new paradigm for the management of the patient with pancreatic cancer,” Dr. Gold said.

The assay still needs to be validated in larger trials, however. He estimated that the assay and related therapies are still 2-3 years from clinical use.

Disclosures: Dr. Gold did not provide a disclosure statement. The study's senior author, Dr. David M. Goldenberg, disclosed that he is the chief scientific officer and chairman of the board of directors for Immunomedics Inc., a biopharmaceutical company that develops monoclonal, antibody-based products for the targeted treatment of cancer and other diseases.

My Take

Earlier Diagnosis Will Save Lives

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (approximately 20% 5-year surgical survival for stage I disease versus 2% for stage IV disease). The problem has always been how to identify the patient with early disease since symptoms may occur late in those with pancreatic cancer.

The recent discovery that circulating blood levels of PAM4 (quantified through use of the monoclonal antibody clivatuzumab) are “relatively unique to pancreatic cancer” and positive in 68% of those with stage I pancreatic cancer raises hopes that we now have a tool that can lead to earlier diagnosis.

We do need to know more about the protein and its false-positive rates, ensuring that it is not prevalent in noncancer patients with chronic pancreatitis, diabetes mellitus, cigarette smoking, and other conditions that predispose to pancreatic cancer. That information and the development of a logical clinical algorithm of how to utilize circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

An investigational immunoassay can accurately identify pancreatic cancer, potentially giving clinicians the ability to identify and treat the disease in its early stages, according to research presented at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium.

The assay uses a monoclonal antibody to hone in on malignant pancreatic cells; for added benefit, investigators are also employing the antibody to deliver targeted radiotherapy to tumor cells.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference.

The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said. The protein is not present in normal pancreatic tissue or in other types of malignancies. It also is rarely detected in pancreatitis, making it highly specific for pancreatic cancer.

In the small study, Dr. Gold and his associates evaluated 68 patients who had undergone surgery for pancreatic cancer. The investigators obtained information about disease stage from surgical notes about the spread of the disease. They also evaluated 19 healthy controls.

The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting all stages of pancreatic cancer.

“The PAM4 blood test is very specific for pancreatic cancer. If the assay is positive, there is a high positive diagnostic likelihood that the patient has pancreatic cancer,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

If validated, the assay would be valuable for the management of patients with the disease. Most patients do not have symptoms until the advanced stages of tumor growth, when cure is unlikely. Currently, only an estimated 5% of patients with pancreatic cancer survive to 5 years, according to the American Cancer Society.

The PAM4 antibody has the potential to be part of an effective therapy as well.

“Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” Dr. Gold explained.

Researchers have already begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy of the tumor cells in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

“By using the combination of early detection and therapy improvements, we hope to be able to come up with a new paradigm for the management of the patient with pancreatic cancer,” Dr. Gold said.

The assay still needs to be validated in larger trials, however. He estimated that the assay and related therapies are still 2-3 years from clinical use.

Disclosures: Dr. Gold did not provide a disclosure statement. The study's senior author, Dr. David M. Goldenberg, disclosed that he is the chief scientific officer and chairman of the board of directors for Immunomedics Inc., a biopharmaceutical company that develops monoclonal, antibody-based products for the targeted treatment of cancer and other diseases.

My Take

Earlier Diagnosis Will Save Lives

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (approximately 20% 5-year surgical survival for stage I disease versus 2% for stage IV disease). The problem has always been how to identify the patient with early disease since symptoms may occur late in those with pancreatic cancer.

The recent discovery that circulating blood levels of PAM4 (quantified through use of the monoclonal antibody clivatuzumab) are “relatively unique to pancreatic cancer” and positive in 68% of those with stage I pancreatic cancer raises hopes that we now have a tool that can lead to earlier diagnosis.

We do need to know more about the protein and its false-positive rates, ensuring that it is not prevalent in noncancer patients with chronic pancreatitis, diabetes mellitus, cigarette smoking, and other conditions that predispose to pancreatic cancer. That information and the development of a logical clinical algorithm of how to utilize circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

An investigational immunoassay can accurately identify pancreatic cancer, potentially giving clinicians the ability to identify and treat the disease in its early stages, according to research presented at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium.

The assay uses a monoclonal antibody to hone in on malignant pancreatic cells; for added benefit, investigators are also employing the antibody to deliver targeted radiotherapy to tumor cells.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference.

The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said. The protein is not present in normal pancreatic tissue or in other types of malignancies. It also is rarely detected in pancreatitis, making it highly specific for pancreatic cancer.

In the small study, Dr. Gold and his associates evaluated 68 patients who had undergone surgery for pancreatic cancer. The investigators obtained information about disease stage from surgical notes about the spread of the disease. They also evaluated 19 healthy controls.

The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting all stages of pancreatic cancer.

“The PAM4 blood test is very specific for pancreatic cancer. If the assay is positive, there is a high positive diagnostic likelihood that the patient has pancreatic cancer,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

If validated, the assay would be valuable for the management of patients with the disease. Most patients do not have symptoms until the advanced stages of tumor growth, when cure is unlikely. Currently, only an estimated 5% of patients with pancreatic cancer survive to 5 years, according to the American Cancer Society.

The PAM4 antibody has the potential to be part of an effective therapy as well.

“Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” Dr. Gold explained.

Researchers have already begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy of the tumor cells in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

“By using the combination of early detection and therapy improvements, we hope to be able to come up with a new paradigm for the management of the patient with pancreatic cancer,” Dr. Gold said.

The assay still needs to be validated in larger trials, however. He estimated that the assay and related therapies are still 2-3 years from clinical use.

Disclosures: Dr. Gold did not provide a disclosure statement. The study's senior author, Dr. David M. Goldenberg, disclosed that he is the chief scientific officer and chairman of the board of directors for Immunomedics Inc., a biopharmaceutical company that develops monoclonal, antibody-based products for the targeted treatment of cancer and other diseases.

My Take

Earlier Diagnosis Will Save Lives

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (approximately 20% 5-year surgical survival for stage I disease versus 2% for stage IV disease). The problem has always been how to identify the patient with early disease since symptoms may occur late in those with pancreatic cancer.

The recent discovery that circulating blood levels of PAM4 (quantified through use of the monoclonal antibody clivatuzumab) are “relatively unique to pancreatic cancer” and positive in 68% of those with stage I pancreatic cancer raises hopes that we now have a tool that can lead to earlier diagnosis.

We do need to know more about the protein and its false-positive rates, ensuring that it is not prevalent in noncancer patients with chronic pancreatitis, diabetes mellitus, cigarette smoking, and other conditions that predispose to pancreatic cancer. That information and the development of a logical clinical algorithm of how to utilize circulating levels of PAM4 as a screening test will be important to determining its future clinical use.