Adjuvant Chemotherapy with Gemcitabine for Resected Pancreatic Cancer

The follow-up results of CONKO-001 randomised trial show increase in overall- and disease-free survival

Among patients with pancreatic cancer with surgically complete removal of the cancer, adjuvant treatment with gemcitabine for 6 months resulted in increased overall survival as well as disease-free survival, compared with observation alone, according to results from an update of the CONKO-001 randomised study, published in the 9 October 2013 issue of JAMA.

The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. The poor prognosis is mainly related to inability to detect the tumour at an early stage, its high potential for early dissemination, and its relatively poor sensitivity to chemotherapy or radiation therapy. Even after complete removal of the tumour, the vast majority of patients relapse within 2 years, leading to a 5-year survival rate of less than 25%. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.

CONKO-001 (Charité Onkologie 001) is a multicenter, open-label, phase III randomised trial that evaluated the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumour resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. The study objective was to analyse whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival.

After stratification for tumour stage, nodal status and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment for 6 months or to observation alone. The primary endpoint was disease-free survival. Secondary endpoints included treatment safety and overall survival, with overall survival defined as the time from date of randomisation to death. Patients lost to follow-up were censored on the date of their last follow-up.

Dr. Helmut Oettle of the Charite-Universitatsmedizin Berlin, Germany, and colleagues led by Dr. Hanno Riess conducted a follow-up of a randomised trial that previously reported improvement in disease-free survival with adjuvant gemcitabine. A total of 368 patients were randomised, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0%) had relapsed. The median follow-up time was 136 months (11.3 years).

The median disease-free survival was 13.4 months in the treatment group compared with 6.7 months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; p < 0.001).

By the end of the follow-up period, 316 patients (89.3%) had died and 38 patients were still alive, 23 in the treatment group and 15 in the observation group. The researchers found a statistically significant difference in overall survival between the study groups, with a median of 22.8 months in the gemcitabine group compared with 20.2 months in the observation group (hazard ratio, 0.76 [95% CI, 0.61-0.95]; p = 0.01). There was also a statistically significant absolute 10.3% improvement in the 5-year overall survival rate (20.7% vs. 10.4%) and a 4.5% improvement in the 10-year survival rate (12.2% vs. 7.7%), compared with observation alone.

The authors concluded that data from this show that among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation resulted in increased overall survival as well as disease-free survival. In addition, they wrote that their findings provide strong support for the use of gemcitabine in this setting.

Trial Registration isrctn.org Identifier: ISRCTN34802808.
The trial was supported in part by a grant from Lilly Germany. The study was further supported by the German Cancer Society and promoted by a research grant from the Charite-Universitatsmedizin Berlin.

Reference:

H. Oettle, P. Neuhaus, A. Hochhaus, et al. Adjuvant Chemotherapy With Gemcitabine and Long-term Outcomes Among Patients With Resected Pancreatic Cancer: The CONKO-001 Randomized Trial. JAMA 2013; 310(14):1473-1481. doi:10.1001/jama.2013.279201.