John P. Neoptolemos, MD
The addition of capecitabine to standard adjuvant gemcitabine nearly doubled 5-year overall survival (OS) rates compared with gemcitabine alone for patients with pancreatic cancer whose tumors were surgically removed, according to a phase III European trial announced at the 2016 ASCO Annual Meeting.
The median OS was 28 months with the combination regimen versus 25.5 months with gemcitabine alone, an improvement of 18% (HR, 0.82; 95% CI, 0.68-0.98; P
= 0.032). While the boost in median OS was modest, it translated to a near-doubling of survival rates at 5 years. In the combination arm, the 5-year OS rate was 29% compared with 16% in the single-agent group.
Based on these findings, the combination regimen will be the new standard of care for patients with resected pancreatic cancer, said lead author John P. Neoptolemos, MD, chair of Surgery in the Department of Molecular and Clinical Cancer Medicine at the University of Liverpool, in England.
“Unfortunately, most patients are not candidates for surgery when they are diagnosed with pancreatic cancer,” Neoptolemos 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.”
There is a rising incidence of pancreatic cancer, with 338,000 cases diagnosed worldwide in 2012 and 331,000 people dying of the disease that year, Neoptolemos said. Pancreatic cancer is the third most common cause of cancer death in the United States, he said, and is expected to cause more deaths this year than breast cancer. He added, though, that there’s a growing disparity between the number of cases diagnosed and the number of deaths from the disease each year, due to more effective treatment with chemotherapy. Investigators embarked on the trial to determine whether a chemotherapy doublet could further boost that trend.
Run by the European Study Group for Pancreatic Cancer, the international, randomized, open-label ESPAC-4 was the second-largest trial ever conducted in patients with the disease who had undergone surgery, including 732 patients at 92 sites in 6 countries. The trial was launched in January of 2008 and concluded in November of 2014.
Patients were randomized 1:1 and treated with either gemcitabine alone or with gemcitabine plus capecitabine within 12 weeks of completing surgery for early-stage pancreatic ductal carcinoma. Treatment with chemotherapy lasted 24 weeks.
Gemcitabine, in addition to being an approved treatment for pancreatic cancer, is approved to treat breast, ovarian and lung cancers. Capecitabine is approved for use in breast and colorectal cancers.
Participants, who were a median 65 years of age and 57% men, were typical of a real-world patient population, with a large proportion having unfavorable prognostic factors, such as locally advanced or aggressive disease, large tumor size or incomplete removal of the tumor. Most patients had an ECOG performance status of 0 or 1, although 3% of them had a performance status of 2, the authors reported in their abstract.
Survival on the combination regimen was not affected by factors such as disease aggressiveness or tumor size, but smokers who quit the habit after their diagnoses fared better than those who did not stop smoking.
The types and severity of adverse events were similar between the two study groups, although severe diarrhea and fatigue were somewhat more common in the combination arm of the trial. Quality of life was also similar between groups.
Next steps will involve testing the dual regimen in combination with additional drugs to see if those groupings lead to better effectiveness. Future research efforts will also focus on developing tests to determine which patients with pancreatic cancer are most likely to benefit from various potential treatments after surgery, according to the organization.
“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,” said Smitha Krishnamurthi, MD, a medical oncologist at UH Case Medical Center, and associate professor, medicine, Case Western Reserve University School of Medicine and an ASCO expert in pancreatic cancer.
Neoptolemos JP, Palmer D, Ghaneh P, et al. ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine and capecitabine versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. Presented at: the 2016 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2016; Chicago, Ill. Abstract LBA4006.<<< View more from the 2016 ASCO Annual Meeting