Adding capecitabine chemotherapy to gemcitabine after pancreatic cancer resection was associated with longer overall survival (OS) than gemcitabine chemotherapy alone, according to results from the European Study Group for Pancreatic Cancer (ESPAC)-4 clinical trial. For the small proportion of patients with pancreatic cancer who are candidates for surgery, adjuvant gemcitabine chemotherapy is the current standard of care worldwide, said John P. Neoptolemos, MD, Chair of Surgery, University of Liverpool, United Kingdom, during an oral abstract session at the 2016 American Society of Clinical Oncology annual meeting. “We thought that the combination of gemcitabine plus capecitabine…may be better than gemcitabine alone, and launched the phase 3 ESPAC-4 trial,” he stated.
Reviewing the slow progress toward longer 5-year survival in pancreatic cancer, Dr Neoptolemos noted that pancreatic cancer is the third most common cause of cancer death in the United States. The incidence and death rate of pancreatic cancer are rising—an estimated 41,780 people will die from pancreatic cancer in the United States in 2016.
From the early 1970s to 2010, the 1-year survival in patients with pancreatic cancer who lived in the United Kingdom increased from 10% to 21%; this was attributed to the increased use of chemotherapy. According to Dr Neoptolemos, previous ESPAC clinical trials showed that the 5-year survival rate in patients with pancreatic cancer was 8% for patients undergoing surgery alone, 11% for patients undergoing chemoradiation and surgery, and 16% to 18% for patients undergoing surgery plus 5-fluorouracil (5-FU) or gemcitabine, with gemcitabine having lower toxicity than 5-FU.
Investigating whether the addition of oral capecitabine to intravenous gemcitabine would lead to better outcomes than gemcitabine alone, ESPAC-4 was conducted at 92 sites in 6 European countries involving 730 patients with resected pancreatic ductal adenocarcinoma. The patients’ median age was 65 years (57% male), and the World Health Organization performance status was 0, 1, or 2 in 42%, 55%, and 3% of patients, respectively. The median maximal tumor size was 30 mm. Participants were randomized to 6 months of gemcitabine (N = 366) or gemcitabine plus capecitabine (N = 364) within 12 weeks of surgery. The primary end point was OS.
A large proportion of the patients had unfavorable prognostic factors, such as locally advanced or aggressive disease, large tumor size, or incomplete tumor resection, said Dr Neoptolemos. The patients were representative of a real-world patient population with pancreatic cancer, he added.
The median OS was 28 months with gemcitabine plus capecitabine compared with 25.5 months with gemcitabine alone (hazard ratio, 0.82; 95% confidence interval, 0.68-0.98; P = .032). The estimated 5-year survival increased significantly to 28.8% with gemcitabine plus capecitabine versus 16.3% with gemcitabine alone.
“The difference in median survival may seem modest, but the improvement in long-term survival is substantial for this cancer,” said Dr Neoptolemos. He reiterated that the 5-year survival with surgery alone is approximately 8%.
Serious adverse events were reported in 107 patients who received gemcitabine alone and in 109 patients who received the combination; treatment-related adverse events were similar between the 2 arms: 94 (26%) versus 86 (24%), respectively. Overall, toxicities were manageable and acceptable.
“There was no difference between the 2 arms, and this is important given the fact that one arm is combination chemotherapy,” Dr Neoptolemos said at a press conference at the meeting. This combination is a new standard of care, he said. “These findings are significant, because they show that those patients who can undergo surgery have a fighting chance of surviving this cancer with the combination of 2 commonly used chemotherapies,” Dr Neoptolemos concluded.
Commenting at the press conference, pancreatic cancer expert Smitha Krishnamurthi, MD, said, “Pancreatic cancer remains one of the most hard-to-treat cancers. It is a major win to find that adding a generic chemotherapy not only improves survival for these patients, but does so with little effect on patients’ quality of life.”
