Identification of a KRAS mutation in a patient with non-small cell lung cancer treated with chemoradiotherapy and panitumumab

Cancer Biol Ther. 2013 Oct 1;14(10):883-7. doi: 10.4161/cbt.25942. Epub 2013 Aug 2.

Abstract

RTOG 0839 is a Phase II study of pre-operative chemoradiotherapy with or without panitumumab in potentially operable locally advanced non-small cell lung cancer (NSCLC). The investigational agent, panitumumab, is an anti-epithelial growth factor receptor (EGFR) antibody that improves progression-free survival in chemorefractory metastatic colorectal cancer (mCRC). Recently, both KRAS mutational status (i.e., mutated or not) and subtype (i.e., activating or inactivating) have been shown to be predictive of response to anti-EGFR therapy in mCRC. However, in NSCLC, it is unknown if KRAS mutational status or subtype predict benefit to anti-EGFR therapies because of unique genetic and epigenetic factors unique to each cancer. We present a patient with stage III NSCLC containing a KRAS G12D activating mutation who had a partial pathologic response, with disappearance of a minor KRAS mutant clone. This case suggests possible eradication of the G12D KRAS lung cancer clones by concurrent chemoradiation with panitumumab.

Keywords: EGFR; KRAS; biomarker; non-small cell lung cancer; panitumumab.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Base Sequence
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Chemoradiotherapy
  • DNA Mutational Analysis
  • Female
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / therapy
  • Middle Aged
  • Mutation, Missense*
  • Paclitaxel / administration & dosage
  • Panitumumab
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Radiography
  • Treatment Outcome
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Panitumumab
  • Carboplatin
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Paclitaxel