Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer

Br J Cancer. 2015 Jul 14;113(2):199-203. doi: 10.1038/bjc.2015.215. Epub 2015 Jun 30.

Abstract

Background: Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825).

Methods: Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations.

Results: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations.

Conclusion: Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Codon*
  • Docetaxel
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Taxoids / administration & dosage
  • ras Proteins / genetics*

Substances

  • AZD 6244
  • Benzimidazoles
  • Codon
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Taxoids
  • Docetaxel
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins

Associated data

  • ClinicalTrials.gov/NCT00890825