Immunoassay Might Aid Early Detection Of Pancreatic Cancer

An investigational monoclonal antibody can be used to identify early-stage pancreatic cancer, researchers reported.

“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 in advance of presentation of the findings at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium. The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said.

The researchers analyzed data on about 68 patients who had undergone surgery for pancreatic cancer, and 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 pancreatic cancer.

The PAM4 antibody also has the potential to be part of an effective therapy. “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,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

Researchers have begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy 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.

Dr. Gold estimated that the assay and related therapies are 2-3 years from clinical use.

Disclosures: Senior author Dr. David Goldenberg is the chief scientific officer and chairman of the board of directors for Immunomedics, which develops monoclonal antibody–based treatments. Dr. Gold did not provide a disclosure statement.

My Take

Hope for Earlier Diagnosis

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (about 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.

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 will have a tool for earlier diagnosis.

We need to know more about the protein and the false-positive rates, to ensure 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 an algorithm for assessing circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

An investigational monoclonal antibody can be used to identify early-stage pancreatic cancer, researchers reported.

“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 in advance of presentation of the findings at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium. The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said.

The researchers analyzed data on about 68 patients who had undergone surgery for pancreatic cancer, and 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 pancreatic cancer.

The PAM4 antibody also has the potential to be part of an effective therapy. “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,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

Researchers have begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy 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.

Dr. Gold estimated that the assay and related therapies are 2-3 years from clinical use.

Disclosures: Senior author Dr. David Goldenberg is the chief scientific officer and chairman of the board of directors for Immunomedics, which develops monoclonal antibody–based treatments. Dr. Gold did not provide a disclosure statement.

My Take

Hope for Earlier Diagnosis

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (about 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.

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 will have a tool for earlier diagnosis.

We need to know more about the protein and the false-positive rates, to ensure 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 an algorithm for assessing circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

An investigational monoclonal antibody can be used to identify early-stage pancreatic cancer, researchers reported.

“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 in advance of presentation of the findings at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium. The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said.

The researchers analyzed data on about 68 patients who had undergone surgery for pancreatic cancer, and 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 pancreatic cancer.

The PAM4 antibody also has the potential to be part of an effective therapy. “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,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

Researchers have begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy 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.

Dr. Gold estimated that the assay and related therapies are 2-3 years from clinical use.

Disclosures: Senior author Dr. David Goldenberg is the chief scientific officer and chairman of the board of directors for Immunomedics, which develops monoclonal antibody–based treatments. Dr. Gold did not provide a disclosure statement.

My Take

Hope for Earlier Diagnosis

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (about 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.

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 will have a tool for earlier diagnosis.

We need to know more about the protein and the false-positive rates, to ensure 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 an algorithm for assessing circulating levels of PAM4 as a screening test will be important to determining its future clinical use.