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Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Purpose Advanced pancreatic cancer (APC), in addition to its high mortality, accounts for the highest rates of venous thromboembolic events (VTEs). Enoxaparin, a low–molecular weight heparin, is effective in prevention and treatment of VTEs. Some small studies have indicated that this benefit might extend to patients with cancer. Patients and Methods Patients with histologically proven APC were randomly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival. Results A total of 312 patients were recruited as one of the protocol end points was reached. Within the first 3 months, the numbers of symptomatic VTEs were as follows: 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group (hazard ratio [HR], 0.12; 95% CI, 0.03 to 0.52; χ2 P = .001). The numbers of major bleeding events were as follows: five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm (HR, 1.4; 95% CI, 0.35 to 3.72; χ2 P = 1.0). Overall cumulative incidence rates of symptomatic VTEs were 15.1% (observation) and 6.4% (enoxaparin; HR, 0.40; 95% CI, 0.19 to 0.83; P = .01). Progression-free (HR, 1.06; 95% CI, 0.84 to 1.32; P = .64) and overall survival (HR, 1.01; 95% CI, 0.87 to 1.38; P = .44) did not differ between groups. Conclusion This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in outpatients with APC. Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting.

281 Background: The role of T lymphocytes, frequently found in the tumor microenvironment, on development and behavior of several solid tumors is well recognized. Studies on breast cancer and colon carcinoma showed the prognostic and predictive impact of tumor infiltrating T lymphocytes (TILs) while there are no similar studies on pancreatic cancer (PC) until now. Methods: We evaluated the prognostic effect of CD8 and CD103 positive TILs in a cohort of PC patients in the CONKO-001 study treated with adjuvant Gemcitabine or observed only. In 165 formalin-fixed paraffin-embedded (FFPE) tissue samples suitable for tissue microarray construction, CD 8 und CD 103 positive TILs were identified by immunohistochemical staining and counted manually; a ratio of intraepithelial to total CD 103 positive TILs was calculated. Results: The mean number of CD8 positive TILs was 69, a high number ( > 42 TILs) of CD8 positive lymphocytes was significantly associated with longer disease-free (DFS) and overall survival (OS) in the overall study population (high vs low median DFS 12.8 vs 7.4 months; p = 0.007, median OS 26.7 vs 18.1 months; p = 0.018). Furthermore, a ratio of intraepithelial to total CD103 positive lymphocytes < 0.3 was associated with significantly improved DFS and OS in the overall study population (high vs low median DFS 6.5 vs 11.8 months; p = 0.031, median OS 16.6 vs 24.7 months; p = 0.009). Conclusions: Our results suggest that the presence of TILs is important for prognosis in resected PC. We showed for the first time a prognostic effect of CD 8 and CD 103 expressing lymphocytes in PC. Therefore, we suggest further analysis of lymphocyte populations in this dismal entity.

e15717Background: The combination of nabpaclitaxel/gemcitabine (AG) is one standard of care treatment for patients (pts) with advanced pancreatic adenocarcinoma (APC). Only insufficient data accord...

e15219 Background: Although recurrences occur after most curatively intended PA resections with ensuing adjuvant G chemotherapies, it remains unclear, whether and from which point in time after adj...

e15218 Background: It remains unclear, whether survival from the initiation of Gem-based first-line therapy differs between previously operated patients with or without adjuvant chemotherapy with Gem and patients receiving palliative therapy after a diagnosis of PC in an initially unresectable disease stage. Methods: We retrospectively analysed prospectively collected data of 702 PC-patients treated at “Charite Campus Virchow-Klinikum” between 1991 and 2014. Kaplan-Meier estimates of the primary endpoints PFS and OS from the initiation of palliative first-line therapy were compared with the aid of log-rank test with two-sided p-values of < 0.05 for 462 patients with Gem-based palliative first-line therapy. Among them, 140 had been operated with curative intent, 45 having, 95 not having received adjuvant therapy; 322 had been treated palliatively after first diagnosis of PC. Prognostic factors of statistical significance were established by Cox regression analysis. Results: PFS and OS were significantly lo...

4044 Background: Patients (pts) with advanced pancreatic cancer (APC) often suffer from symptomatic thromboembolic events (sVTE). The CONKO-004 trial showed that the low molecular weight heparin (LMWH) enoxaparin reduces sVTE (p