CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial

Abstract

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/m 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.

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

“…With 3 years of follow-up, the emerging durability data on OS and DFS in this trial are encouraging when viewed in the context of current literature reporting large-scale trials with gemcitabine as monotherapy, which range from 10.7 to 13 months for DFS, and 17.1 to 26.5 months for median survival. 4,5,[15][16][17][18][19] Based on time from surgery, in this study median DFS was 16.1 months and median OS was 33.3 months for the total study population, which compare favourably with published data for gemcitabine monotherapy, and indeed even with gemcitabine and capecitabine combination therapy (GemCap). Modification of the vaccination schedule, whilst appearing to eliminate the risk of allergic reactions, did not appear to compromise this encouraging efficacy.…”

Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy

“…Targeting this key pro-tumourigenic molecular pathway has been explored in PDAC with the combination of standard therapy gemcitabine and small molecule EGFR inhibitor erlotinib revealing a modest but significant improvement in patient survival in advanced disease [175][176][177]. However, significance was lost when this combination was trialled in all-comers in the adjuvant setting [178]. Further analyses revealed that therapeutic benefit of combined gemcitabine/EGFR inhibition associated with KRAS wild-type tumour status [179,180] or development of skin rash in patients, which represents another measure of EGFR inhibitor activity [181].…”

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer

“…Surgical resection with adjuvant chemotherapy is the current standard of care. Recent trials have reported improved median overall survival to 24·5–28 months with adjuvant treatment. However, these trials did not report how many eligible patients were fit enough to be randomized to receive adjuvant chemotherapy.…”