An immunoassay to detect the presence of PAM4 showed promise for the detection and diagnosis of early-stage pancreatic ductal adenocarcinoma (PDAC) in a multinational study presented at the ASCO 2012 Gastrointestinal Cancers Symposium.

“Pancreatic cancer is almost universally fatal. There are as many deaths each year as there are new cases. The two major reasons for this are that pancreatic cancer is generally not found at an early enough stage for curative procedures, and advanced stage cancers cannot be cured,” explained David V. Gold, PhD, Garden State Cancer Center, Morris Plains, New Jersey.

Early detection can improve survival, he continued. Five-year survival is 2% to 3%; in patients with stage I pancreatic cancer, 5-year survival is 20%.

At the ASCO symposium, Gold coauthored three abstracts related to the PAM4 immunoassay. The first abstract showed that the PAM4 assay is a single-agent diagnostic test. A second abstract found that combining PAM4 with the CA19-9 biomarker immunoassay significantly improved the detection rate for PDAC with good diagnostic accuracy. A third abstract found that the PAM4 antibody can discriminate PDAC from benign chronic pancreatitis at the tissue level using immunohistochemistry.

A study of a serum-based PAM4 antibody test included samples from 298 cases of previously diagnosed PDAC. Among all patients of any stage, 225 were positive (76%) for PAM4; in 28 patients with early stage I PDAC, 18 (64%) were positive. Only 23% of 80 patients with chronic pancreatitis were positive for the antigen.

“Overall, the PAM4-immunoassay detects 76% of patients with all stages of PDAC, and most important, the assay can identify almost twothirds (64%) of patients with early disease, when therapeutic procedures have better opportunities for successful outcomes,” Gold said.

The second study showed that the combined use of PAM4 and CA19-9 immunoassays improved the detection rate for PDAC by about 10%, identifying 84% of patients with all stages of pancreatic adenocarcinoma. A high level of specificity was maintained with the combination of the tests. However, combined use of these assays did not improve the detection of earlystage patients. CA19-9 is approved by the FDA for monitoring pancreatic cancer progression, but as yet, no test is approved for the detection and diagnosis of pancreatic cancer.

The third study included 126 patients with pancreatic disorders other than cancer. PAM4 positivity was found in 19% of patients with benign pancreatic disease and 23% of patients with chronic pancreatitis.

“These results demonstrate that the reactivity of the PAM4 antibody is highly restricted to PDAC. Because of this high specificity, a positive result suggests the cancer is of pancreatic origin,” Gold said.

These results provide a basis for future studies of these biomarkers for surveillance of patients at high risk for PDAC, Gold stated.

The moderator of the press conference, Morton Kahlenberg, MD, University of Texas Health Science Center in San Antonio, said that the new test is quite promising. “We are limited by our inability to readily detect earlier stage pancreatic cancer. There is tremendous promise for this new blood-based test to diagnose pancreatic cancer at an earlier stage.”