ERCC1 Expression-Based Randomized Phase II Study of Gemcitabine/Cisplatin Versus Irinotecan/Cisplatin in Patients with Advanced Non-small Cell Lung Cancer

Cancer Res Treat. 2017 Jul;49(3):678-687. doi: 10.4143/crt.2016.365. Epub 2016 Oct 11.

Abstract

Purpose: We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).

Materials and methods: Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1 every 3 weeks) or IP (irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level.

Results: A total of 279 patients were randomly assigned to the GP (n=139) and IP (n=140) arms, among which 63% were ERCC1-positive and 268 patients were assessable for the RR. The GP and IP arms did not differ significantly with respect to the RR (29.8% vs. 27.0%, respectively; p=0.082), median progression-free survival (PFS; 4.5 months vs. 3.9 months, respectively; p=0.117), and overall survival (OS; 16.5 months vs. 16.7 months, respectively; p=0.313). When comparing the efficacy between the ERCC1-positive and ERCC1-negative groups, there was no significant difference in the RR (GP, 28.2% vs. 32.6%, respectively, p=0.509; IP, 30.2% vs. 21.6%, respectively, p=0.536), median PFS (GP, 4.6 months vs. 5.0 months, respectively, p=0.506; IP, 3.9 months vs. 3.7 months, respectively, p=0.748), or median OS (GP, 18.6 months vs. 11.9 months, respectively, p=0.070; IP, 17.5 months vs. 14.0 months, respectively, p=0.821).

Conclusion: Immunohistochemical analysis of the ERCC1 expression level did not differentiate the efficacy of platinum-based chemotherapy in advanced NSCLC.

Keywords: ERCC1; Non-small-cell lung carcinoma; Platinum.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • DNA-Binding Proteins / genetics*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Endonucleases / genetics*
  • Female
  • Gemcitabine
  • Gene Expression
  • Genes, erbB-1
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • KRAS protein, human
  • Deoxycytidine
  • Irinotecan
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • ERCC1 protein, human
  • Endonucleases
  • Proto-Oncogene Proteins p21(ras)
  • Cisplatin
  • Camptothecin
  • Gemcitabine