Administering chemotherapy prior to and following surgery may extend survival in patients with pancreatic ductal adenocarcinoma compared with postoperative administration alone, according to a recent study published by Cecchini et al in JAMA Oncology. The findings may be encouraging for the 15% to 20% of patients with pancreatic cancer whose tumors are operable.
Background
Pancreatic ductal adenocarcinoma—which accounts for about 90% of pancreatic cancer cases—is an aggressive disease with a high mortality rate. Pancreatic ductal adenocarcinoma is predicted to become the second leading cause of cancer-related mortality in the United States by 2030.
“When the study launched, even with operable pancreatic cancers, 90% of patients were still relapsing and dying from their cancer eventually,” explained lead study author Michael Cecchini, MD, Co-Director of the Colorectal Program at the Center for Gastrointestinal Cancers at the Smilow Cancer Hospital and Yale Cancer Center. “We sought to move chemotherapy up in their treatment regimen and give it before surgery to see if we could improve the outcome for our patients,” he added.
Study Methods and Results
In the recent single-arm phase II trial, researchers assigned 46 patients with pancreatic ductal adenocarcinoma to receive six cycles of a modified FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin) prior to surgery and an additional six cycles of the modified regimen following surgery. They noted that the FOLFIRINOX regimen was approved in 2011 as a first-line treatment for patients with metastatic pancreatic cancer. The modified regimen consisted of slightly lower doses of FOLFIRINOX to improve tolerability, which was shown in a 2016 study not to adversely affect outcomes.
The researchers utilized advanced techniques to monitor the progress of treatment, including analyzing circulating tumor DNA (ctDNA) and using the cancer biomarker keratin 17 to help predict patient outcomes. For instance, the patients with detectable ctDNA 4 weeks postsurgery had worse progression-free survival compared with those who had no detectable ctDNA.
The 12-month progression-free survival rate was 67%, indicating significant progress in the management of pancreatic ductal adenocarcinoma. Further, 59% of the patients survived for at least 2 years following completion of the full chemotherapy regimen. The researchers reported that 80.4% (n = 37) of the patients completed all six cycles of chemotherapy prior to surgery and 58.7% (n = 27) of them had successful tumor resection.
Conclusions
Larger randomized clinical trials may be needed to better understand the benefit of FOLFIRINOX prior to surgery in patients with operable pancreatic ductal adenocarcinoma.
“I think even though there have been changes in standard of care for patients with this aggressive pancreatic cancer type, we have here very promising data to justify a larger study,” concluded Dr. Cecchini.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
