No Additional Benefit Of Erlotinib In Adjuvant PDAC Setting

Adjuvant treatment with erlotinib plus gemcitabine does not improve disease-free or overall survival in patients with R0 resected pancreatic ductal adenocarcinoma

medwireNews: Adding erlotinib to adjuvant gemcitabine does not improve survival in patients with pancreatic ductal adenocarcinoma (PDAC) who have undergone an R0 resection, the phase III CONKO-005 trial indicates.

After a median follow-up of 54 months, median disease-free survival (DFS) was an identical 11.4 months for the 219 patients randomly assigned to receive open-label erlotinib 100 mg/day in addition to gemcitabine 1000 mg/m2 given on days 1, 8 and 15 of a 4-week cycle and for the 217 given gemcitabine alone, where both groups received up to six cycles of the allocated regimen.

Overall survival (OS) also did not differ significantly between treatment arms, at a median of 24.5 months for the erlotinib plus gemcitabine group and 26.5 months for the gemcitabine monotherapy group.

The estimated 5-year DFS rates were a comparable 13% and 11%, respectively, but there was a trend favouring the combination arm in terms of long-term survival, with 5-year OS rates of 25% versus 20% for the combination and monotherapy groups, the researchers report.

Outlining the rationale for undertaking the trial, they explain that the addition of the Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor to gemcitabine has shown a marginal but statistically significant OS benefit in patients with nonresectable PDAC, leading to the approval of the combination in the USA and Europe.

However, as seen in patients with stage II and III colorectal cancer, it appears that “EGFR inhibition is effective in metastatic disease but not in the adjuvant setting”, Marianne Sinn, from Charité–Universitätsmedizin Berlin in Germany, and team write in the Journal of Clinical Oncology.

They believe that the role of EGFR inhibition in the PDAC setting “remains poorly understood”, with a need to define the subgroups that benefit most from treatment with anti-EGFR agents.

In the current trial, there was no difference in survival between the treatment arms regardless of whether participants were classified by tumour size or grade, lymph node involvement, Karnofsky performance or study centre.

But Marianne Sinn et al comment that “[o]ngoing analysis of tumor tissue samples of the CONKO-005 trial will hopefully identify a molecular subset of patients with PDAC for whom EGFR inhibition provides maximum benefit.”

Reference

Sinn M, Bahra M, Liersch T, et al. 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. J Clin Oncol; Advance online publication 17 August 2017. doi: https://doi.org/10.1200/JCO.2017.72.6463