Data gleaned from these early clinical trials sets the stage for larger trials in which doctors can compare the safety and effectiveness of a new approach against current standards. In pancreatic cancer, these early-stage trials help move the needle in the right direction by finding ways to improve survival.
This research focus was just one among three important subject areas discussed during the second day of plenary sessions of the AACR’s special conference on pancreatic cancer held on Sunday, September 8th. Researchers also discussed the molecular basis of cancer with presentations on the RAS and oncogene signaling pathways. Over the last several years, there has been increasing interest along with a much better understanding of the very complex signaling pathways that form the basis of tumor formation. This new knowledge can potentially lead to new forms of targeted treatment. Sunday’s session also included important information on early detection and prevention. While breast, colorectal, cervical, and prostate cancer patients have greatly benefitted from early detection methods, pancreatic cancer is most often found at later stages, when surgery is no longer an option. Yet, significant inroads are being made in early detection and prevention for a subset of patients.
Early-Stage Trials and Novel Treatment Combinations
Robert H. Vonderheide, M.D., D.Phil., of the University of Pennsylvania Abramson Cancer Center (Philadelphia), presented “CD40 immunotherapy for pancreatic cancer.” The most promising immunotherapy approaches in pancreas cancer seem to be in combining different treatments. One such three-pronged approach involves combining what is called a CD40 antibody, which boosts the immune system, a checkpoint inhibitor drug, which takes the brakes off the immune system, along with chemotherapy. The hope is these agents work together to fight the cancer. Numerous pharmaceutical companies have developed antibodies designed to activate CD40. Vonderheide discussed some of the clinical trials using these CD40 antibodies, including an ongoing phase II trial combining gemcitabine/nab-paclitaxel with CD40 antibody with or without PD-1 checkpoint inhibitor in metastatic pancreatic cancer patients. Results will be available soon. Another trial is testing pre-operative CD40 plus chemotherapy for patients with newly diagnosed resectable pancreatic cancer. Clinical endpoints have not yet been reported.
RAS and Oncogene Signaling
A gene called p53 has been much the subject of ongoing research because of its significant role in generating tumor-suppressing proteins. Very simply, it’s a powerful ally in stopping tumors from growing. Laura Attardi, Ph.D., of Stanford University School of Medicine (Palo Alto, California), presented “Deciphering the origins of PDAC development.” Her work focuses on p53 and the role it plays in cell death and tumor suppression. p53 is the most frequently mutated gene in human cancer, and the resulting loss of p53 removes a critical barrier to tumor development. Attardi discussed how certain tumors can grow in the absence of p53 mutation, and how those tumors differ from tumors lacking p53 activity. She shows that KRAS activation alone can induce pancreatic tumor growth in mice, although it occurs more slowly than when there is also a loss of p53 activity.
Prevention and Early Detection
Finding ways to prevent and detect pancreas cancer in its earliest, most treatable stage is a vital research focus and it’s these efforts that Anirban Maitra, MBBS, of The University of Texas MD Anderson Cancer Center (Houston), discussed with his presentation “Early detection of pancreatic cancer: Challenges and opportunities.” Pancreatic cancer patients diagnosed at stage IA experience a median survival of 25 months, while those diagnosed at stage IV only experience a median survival of three months. Unfortunately, only about 5 percent of patients are diagnosed at stage IA/B. Maitra discussed the current strategies being developed with the aim of detecting pancreatic cancer earlier, when it’s most treatable and when patients have the best chance of longer-term survival. Roughly 10 percent of pancreatic cancer patients have germline mutations that can be passed on to their children, so the current recommendation is that every patient with confirmed pancreatic cancer should undergo germline testing.