Six months of gemcitabine therapy increased both overall and disease-free survival in patients who had macroscopically complete removal of pancreatic cancer, according to results from a randomized phase III trial reported online Oct. 8 in JAMA.
The study findings support the use of gemcitabine in clinical practice and as the backbone for future studies of adjuvant therapy following resection of pancreatic cancer, said Dr. Helmut Oettle, of the department of medical oncology and hematology, Charité Medical University Berlin, and his associates.
The open-label study involved 368 adults who had undergone complete, curative-intent resection of pancreatic cancer at 88 medical centers in Germany and Austria over a 6-year period. The intention-to-treat analyses included 354 eligible patients, of whom 179 were randomly assigned to receive six cycles of gemcitabine every 4 weeks as outpatients (three weekly infusions followed by a 1-week break), and 175 were assigned to observation-only following a similar schedule of visits.
Disease progression was monitored using abdominal CT, MRI, or ultrasound every 8 weeks. Patients also were assessed for adverse events, performance status, and quality of life every 8 weeks for up to 5 years or until death.
During a median follow-up of 11 years, there were 308 recurrences of pancreatic cancer in 354 patients (87% of the entire study population).
The primary endpoint, disease-free survival, was significantly greater for patients who received gemcitabine (13.4 months) than for the control group (6.7 months), Dr. Oettle and his associates reported (JAMA 2013;310:1473-81).
Rates of disease-free survival also were significantly greater with gemcitabine, compared with controls, at specific time points: 5-year rates were 16.6% vs. 7.0%, respectively, and 10-year rates were 14.3% vs. 5.8%, respectively.
Adjuvant gemcitabine therapy also significantly improved overall survival. At the end of follow-up, 316 patients (89.3%) had died. Median overall survival was 22.8 months with gemcitabine, compared with 20.2 months with observation alone.
This significant difference also persisted at specific time points. Overall survival at 5 years was 20.7% in the gemcitabine group vs. 10.4% in the control group, and at 10 years was 12.2% vs. 7.7%, respectively.
These treatment benefits occurred across all subgroups of patients and regardless of tumor stage or nodal status at the time of resection.
The study findings are likely to be applicable to patients in general clinical practice in many countries, since this was a community-based trial that involved community-based oncology practices as well as academic centers, and there were no uniform standards for surgery, Dr. Oettle and his associates said.
Their research group is now testing gemcitabine monotherapy against gemcitabine combination therapy in similar patients, they added.
The trial was supported by Eli Lilly, the German Cancer Society, and Charité Medical University Berlin. Dr. Oettle reported ties to Roche Pharma, Cellgene, and Fresenius, and his associates reported ties to Bayer, Bristol-Myers Squibb, and other companies.