• hENT1 RNA and protein in combination may act as predictive biomarkers for survival for patients treated with adjuvant gemcitabine in pancreatic cancer

      Hale, J; Evans, A; Aughton, K; Elander, NO; Ghaneh, P; Neoptolemos, JP; Jackson, R; Cox, TF; Campbell, F; Halloran, CM; et al. (2019)
    • Patterns of recurrence after resection of pancreatic ductal adenocarcinoma: a secondary analysis of the ESPAC-4 randomized adjuvant chemotherapy trial

      Jones, RP; Psarelli, EE; Jackson, R; Ghaneh, P; Halloran, CM; Palmer, DH; Campbell, F; Valle, Juan W; Faluyi, O; O'Reilly, DA; et al. (2019)
      IMPORTANCE: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear. OBJECTIVE: To define patterns of recurrence after adjuvant chemotherapy and the association with survival. DESIGN, SETTING, AND PARTICIPANTS: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019. INTERVENTIONS: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine. MAIN OUTCOMES AND MEASURES: Overall survival, recurrence, and sites of recurrence. RESULTS: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P?=?.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P?=?.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P?=?.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P?=?.85 and P?=?.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P?=?.03). CONCLUSIONS AND RELEVANCE: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.
    • TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas (CT TG01-01): a single-arm, phase 1/2 trial

      Palmer, DH; Valle, Juan W; Ting, MY; Faluyi, O; Neoptolemos, JP; Jensen, GT; Iversen, B; Amund, EJ; Moller, AS; Aksnes, AK; et al. (2020)
      BACKGROUND: TG01 is the first cancer immunotherapy targeting KRAS oncogenic mutations. This study assessed the safety and efficacy of TG01/GM-CSF in patients with resected pancreatic adenocarcinoma. METHODS: Patients with stage I or II pancreatic adenocarcinoma who had undergone surgical resection (R0 or R1) received adjuvant gemcitabine with TG01/GM-CSF using two schedules of vaccination. Immune response was defined as a positive delayed-type hypersensitivity (DTH) response and/or positive T-cell proliferation assay. RESULTS: Thirty-two patients were enrolled between February 2013 and May 2016. Nineteen were treated with the high antigen burden, with four serious adverse reactions considered possibly related to TG01 treatment, including three allergic reactions. On this basis, a further 13 patients received a modified vaccination schedule with reduced antigen burden, with no serious adverse events related to TG01. Ninety-five percent patients in the main cohort and 92% in the modified cohort had a positive immune response. Median overall survival (OS) was 33.1 months, and median disease-free survival (DFS) was 13.9 months for the main cohort. For the modified cohort, the median OS was 34.3 months and median DFS was 19.5 months. CONCLUSIONS: TG01/GM-CSF with gemcitabine was well tolerated, with high levels of immune activation. OS and DFS compare favourably with published data for adjuvant gemcitabine. CLINICAL TRIAL REGISTRATION: This clinical trial was registered at ClinicalTrials.gov (NCT02261714).