The prognosis for patients with pancreatic cancer is poor, even for patients with surgically resectable tumors. Gemcitabine (Gemzar) is the standard chemotherapy for advanced pancreatic cancer. Despite the lack of a clear consensus, gemcitabine has also become the mainstay of adjuvant treatment for this deadly disease, even though its effects on survival after surgery have not been demonstrated. Now, findings from the extended follow-up of the Charité Onkologie 001 (CONKO-001) trial of patients with pancreatic cancer who underwent surgery provide support for the use of gemcitabine in the adjuvant setting (Oettle H, et al. JAMA. 2013;310:1473-1481).
CONKO-001 was a multicenter, open-label, parallel-group, randomized, phase 3 trial that compared gemcitabine with observation alone in the adjuvant setting in 368 adults who had undergone complete, curative-intent resection of pancreatic cancer at 88 medical centers in Germany and Austria. In the intent-to-treat analysis, the investigators randomized 354 eligible patients to adjuvant gemcitabine (N = 179) or to observation alone (N = 175). Gemcitabine was administered at 1 g/m2 on days 1, 8, and 15 every 4 weeks for 6 months.
The enrollment period ran from July 1998 to December 2004, and the follow-up period ended September 2012. During a median follow-up of 11 years, pancreatic cancer recurred in 308 patients—145 in the gemcitabine group and 163 in the observation group. The primary end point was disease-free survival (DFS). The secondary end points included overall survival (OS).
The results show that the median DFS was significantly greater with gemcitabine than with observation alone (13.4 vs 6.7 months, respectively). Furthermore, the rates of DFS were significantly better with gemcitabine than with observation at 5 years (16.6% vs 7.0%, respectively) and 10 years (14.3% vs 5.8%, respectively). At the end of the follow-up, 316 of the 354 patients (89.3%) had died. The median OS was 22.8 months in the gemcitabine group versus 20.2 months in the observation group. The difference in OS between the 2 groups was significant. OS in the gemcitabine group at 5 years was 20.7% versus 10.4% in the observation group, and at 10 years it was 12.2% versus 7.7%, respectively. These treatment benefits occurred across all subgroups of patients, regardless of tumor stage and nodal status at the time of resection.
The significant differences in DFS and OS between the treatment groups support the use of gemcitabine in clinical practice and as the backbone for future studies of adjuvant therapy after the resection of pancreatic cancer. These findings are likely to be representative of general clinical practice in other countries, because CONKO-001 was a community-based trial that involved academic centers and community-based oncologists without uniform standards for surgery. The researchers are currently testing gemcitabine monotherapy against gemcitabine combination therapy in similar patients.
