Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP)

Background: To investigate whether addition of cetuximabto standard adjuvant chemotherapy with gemcitabineimproves outcome in pancreatic cancer, specifically whether the rate of disease-free survival (DFS) at 18 months (primary end point) exceeds the previously reported 35% of gemcitabinealone. Patients and methods: Prospective, open-label, multicenter, nonrandomized phase II study in 76 patients with R0- or R1-resected ductal adenocarcinoma of the pancreas included between October 2006 and November 2008. Gemcitabineand cetuximabwere administered for 24 weeks. Secondary end points included overall survival (OS) and toxic effect. Results: Seventy-three patients received cetuximab. Median DFS was 10.0 [95% confidence interval (CI) 8.9–13.6] months and the DFS rate at month 18 of 27.1% (16.7%–37.6%) was inferior to 35%. Median OS was 22.4 (18.2–27.9) months. Subgroup analyses revealed a nonsignificant increase in DFS for patients with versus without skin toxic effect ≥grade 2 (median 14.7 versus 8.3 months, P = 0.073) and wild-type versus mutated K-Ras (median 11.5 versus 9.3 months, P= 0.57). Grade 3/4 toxic effects included neutropenia (11.0%), thrombopenia (7%), skin toxic effect (7%) and allergic reactions (7%). Conclusion: Addition of cetuximabto adjuvant gemcitabinedoes not seem to improve DFS or OS of unstratified pancreatic cancer patients. Trends for improved DFS in patients with wild-type K-Ras and skin toxic effect remain to be