Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial

Oncotarget. 2015 Jul 20;6(20):18162-73. doi: 10.18632/oncotarget.4216.

Abstract

Objective: To analyze the efficacy of gemcitabine with or without erlotinib for pancreatic cancer, and to determine the predictive role of epidermal growth factor receptor (EGFR) and KRAS mutations in these patients.

Methods: This was a single-center, randomized, open-label, prospective trial. Eighty-eight chemotherapy-naïve metastatic pancreatic cancer patients were randomized for treatment with gemcitabine or gemcitabine plus erlotinib. EGFR and KRAS mutations were analyzed, respectively. The primary endpoint was the disease control rate.

Results: Disease control rate (64% vs. 25%; P < 0.001), progression-free survival (median 3.8 vs. 2.4 months; P < 0.001), and overall survival (median 7.2 vs. 4.4 months; P < 0.001) were better in the gemcitabine plus erlotinib group than in the gemcitabine alone group. In the gemcitabine plus erlotinib group, disease control (85% vs. 33%; P = 0.001), progression-free survival (median 5.9 vs. 2.4 months; P = 0.004), and overall survival (median 8.7 vs. 6.0 months; P = 0.044) were better in patients with EGFR mutations than in those without EGFR mutations. KRAS mutation was not associated with treatment response or survival.

Conclusions: Gemcitabine plus erlotinib is more effective than gemcitabine alone for treating metastatic pancreatic cancer patients, especially those with EGFR mutations. ClinicalTrials.gov number, NCT01608841.

Keywords: adenocarcinoma; epidermal growth factor receptor; erlotinib; pancreas.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • DNA Mutational Analysis
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride / adverse effects
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Gemcitabine
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prospective Studies
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Taiwan
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Deoxycytidine
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT01608841