Oncologists may have an important new weapon in battling pancreatic cancer and it is already on the pharmacy shelf.
Researchers at Memorial Sloan Kettering Cancer Center in New York, NY, have found that perioperative treatment with the agent pasireotide may significantly decrease the rate of postoperative pancreatic fistula, leak, and abscess.
They conducted a single-center, randomized, double-blind trial with 300 patients and found that the patients who received pasireotide had a 9% rate of grade 3 or higher postoperative pancreatic fistula, leak, or abscess compared with that of 21% patients in the placebo group.1
“We were certainly very pleased with the results because it was a really dramatic response,” said lead study investigator Peter Allen, MD, who is the associate director of the Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center. “It cut the rate of leaks in half, and that is a fairly dramatic result.”
Postoperative pancreatic fistula is a major cause of morbidity and mortality associated with pancreatic resection. Dr. Allen said that as many as 2% to 4% of patients do not survive surgery because of complications. It is hoped that pasireotide is a game changer.
Pasireotide, which is approved for patients who have Cushing’s disease and have failed surgery or are ineligible for surgical approaches, is a somatostatin analogue that decreases pancreatic exocrine secretions. It has a longer half-life and a broader binding profile than octreotide. Previous studies with octreotide for treating postoperative pancreatic fistula produced mixed results.
“This new agent has tremendous promise in reducing a major problem with pancreatic surgery. Current agents, such as octreotide, have been studied and found to be ineffective in reducing the rate of pancreatic fistula. However, this novel agent works much better than octreotide and the findings of the single-center study are very encouraging. If this agent is found to work as well across multiple institutions and patient cohorts as it did at Memorial Sloan Kettering, it could be a game changer,” Ryan Fields, MD, an assistant professor of surgery at Washington University School of Medicine in St. Louis, MO, told Cancer Therapy Advisor.
Rebecca M. Minter, MD, who is an associate professor of surgery at the University of Michigan Health System in Ann Arbor, MI, said that the data from this new study are quite compelling and she noted that pasireotide has a good side-effect profile.
“Because it is so safe, it can be used widely,” said Dr. Minter in an interview with Cancer Therapy Advisor. “Based on its toxicity, it should be rolled out pretty quickly. We don’t have anything else to use now to treat pancreatic fistula.”
Dr. Minter said more research is warranted and that the findings from this study will have to be confirmed at other institutions. However, she believes, based on these new findings, clinicians may want to consider using this agent perioperatively now rather than postoperatively. Steven Hochwald, MD, who is chief of gastrointestinal surgery at Roswell Park Cancer Institute, in Buffalo, NY, does not agree with Dr. Minter.
Dr. Hochwald believes it is premature to widely adopt this treatment for pancreatic fistula. “The study was well done due to its randomized nature, and the study size was reasonable,” Dr. Hochwald told Cancer Therapy Advisor. “However, the results do require confirmation with other well done studies using pasireotide before this treatment is widely adopted.”
Allen et al1 randomly assigned 152 patients to receive 900 ug of subcutaneous pasireotide twice daily beginning preoperatively on the morning of surgery and continuing for 7 days (14 doses) while 148 patients received placebo.
The primary endpoint for the study was the development of fistula, leak, or abscess of grade 3 or higher (requiring drainage) and the researchers found that it occurred in 45 out of 300 patients (15%). However, the rate of grade 3 or higher occurred in only 9% of patients receiving pasireotide compared with 21% of placebo patients.
In addition, the findings were consistent among patients undergoing pancreaticoduodenectomy, distal pancreatectomy, a dilated pancreatic duct, and a nondilated pancreatic duct.
Dr. Allen said pancreatic leaks are the Achilles’ heel of these surgeries and eliminating them may improve outcomes. It is hoped that this agent may be able to block leakage at the secretion source by binding to receptors in pancreatic cells and blocking the secretion of digestive enzymes.
He said that the pancreas can secrete up to a liter of fluid a day, so when it leaks into the abdominal cavity, it can build up quickly. In this study, readmission rates were 17% in the pasireotide arm compared with 29% in the placebo arm.
Boris Kuvshinoff II, MD, MBA, who is the director of the Liver and Pancreas Tumor Center at Roswell Park Cancer Institute in Buffalo, NY, said cost may be an issue for clinicians who now decide to start using this agent immediately for treating pancreatic fistula.
“The drug is only approved in the United States as an orphan drug for refractory Cushing’s. This would make it off-label use and could be expensive, [which] might be a barrier to using this drug on a routine basis for this indication,” Dr. Kuvshinoff told Cancer Therapy Advisor.
- Allen PJ, Gönen M, Brennan MF, et al. Pasireotide for postoperative pancreatic fistula. N Engl J Med. 2014;370(21):2014-2022.