Pancreatic Cancer Report Urges Changes in Clinical Trials
The slow but steady march toward more individualized care in cancer medicine has left pancreatic cancer behind. Patients diagnosed with this disease live no longer today than patients diagnosed 2 decades ago, despite more than a dozen large clinical trials. Even as many patients with other cancers have benefited from targeted drugs like imatinib (Gleevec) and trastuzumab (Herceptin), pancreatic cancer remains as deadly as ever.
Recent advances in science and a new study may suggest a way forward. An expert panel convened by NCI has issued a consensus report that discusses many aspects of developing and testing treatments in this disease and charts a course for the next 5 years.
"This report is a call to action," said lead author Dr. Philip A. Philip of the Barbara Ann Karmanos Cancer Institute in Detroit, MI. "We need to do better clinical trials that are based on solid science, and patients need to be encouraged to participate in these studies."
A central recommendation is to design pilot studies that test potential treatments in smaller groups before proceeding to the kinds of large trials that have yielded disappointing results in the past. Decisions about which molecular targets and potential drugs to pursue will be made based on scientific evidence that will include preclinical and animal studies that better represent pancreatic cancer in humans.
"We have to be more thoughtful and innovative in bringing forward new targeted therapies and treatment combinations," said Dr. Philip. The hope is that the new strategy will ensure that precious resources and patient time are spent on the most promising treatments.
Often detected only after the disease has spread, pancreatic cancer is the fourth deadliest cancer in the United States, though it is not nearly as common as many other cancers. Most patients die within a year of diagnosis, and conventional chemotherapy has been notoriously unable to improve survival. With the exception of erlotinib (Tarceva), which has only a marginal benefit, the targeted drugs tested to date, including angiogenesis inhibitors, have not performed well.
The challenge for the field is to develop treatments when knowledge of pancreatic cancer biology is still limited. As the report notes, a better understanding of the complex signaling pathways in pancreatic tumors and the role of the local tumor environment are needed. More sophisticated modeling systems and repositories of high-quality biological samples that can be shared among preclinical researchers are also essential, noted Dr. Jack Welch, who oversees NCI's portfolio of gastrointestinal clinical trials in the Division of Cancer Treatment and Diagnosis.
"This is a difficult disease, and the scale of the challenge requires a broad-based and cooperative effort," Dr. Welch added. "To develop the kinds of combination treatments envisioned in the report, the pharmaceutical industry, researchers, and regulatory agencies will need to cooperate at an early stage and show flexibility."
The report stems from a 2007 meeting organized by the NCI Gastrointestinal Cancer Steering Committee, which brought together researchers, clinicians, patient advocates, and representatives from the pharmaceutical industry. The "Consensus Report of the National Cancer Institute Clinical Trials Planning Meeting on Pancreas Cancer Treatment" appeared online October 26 in the Journal of Clinical Oncology (JCO).
Also published in that issue of JCO was a study that provides an example of the kinds of trials many in the field hope to avoid in the future. As has been the pattern for these studies, patients saw little or no benefit from the experimental treatment, in this case a combination of gemcitabine (Gemzar) and capecitabine (Xeloda), as compared with gemcitabine alone.
The study, by the Medical Research Council in the United Kingdom, did not find an improvement in overall survival with the drug combination compared with gemcitabine alone. By another measure, however, there was a statistically significant difference: The combination delayed the time the disease took to progress by a little less than a month.
"You don't have to be a doctor to see that the difference between the two arms of this study is miniscule and of no real clinical benefit," commented Dr. Philip. "We need to make a distinction between what is statistically significant and what is meaningful for our patients."
According to an accompanying editorial in JCO, many groups involved in clinical trials for pancreatic cancer have learned the historic lessons of limited success in large trials and have already begun to adopt new ideas about developing and testing treatments. The authors stress that the report's recommendations be strongly considered in any clinical trial being planned for this disease.
Dr. Andrew Lowy, a surgical oncologist at the University of California, San Diego, and co-author of the report, is optimistic about the next few years. "We now have a greater understanding of this disease than ever before and more new agents directed at targets that have been rationally identified," he wrote in an e-mail.
"Awareness of pancreatic cancer in the community is growing, and groundswells of public support generally lead to increases in funding for research," he continued. "This will only help our progress."
—Edward R. Winstead