Correlation between KRAS mutation status and response to chemotherapy in patients with advanced non-small cell lung cancer☆.

Objectives: KRAS mutations are the most commonly found mutations in patients with non-small cell lung cancer (NSCLC) adenocarcinoma histology. The clinical implications of KRAS mutations in patients with advanced NSCLC are not well defined. We sought to determine if there is a correlation between KRAS mutation status, response to cytotoxic chemotherapy, and survival in patients with metastatic or recurrent NSCLC.

Materials And Methods: Patients with metastatic or recurrent NSCLC and tumor mutation analyses were analyzed for response to conventional chemotherapy. The presence or absence of tumor mutations was assessed with the SNaPshot assay, which detects >40 somatic mutations in eight genes, including KRAS. ALK fluorescence in-situ hybridization analysis was done separately. Associations between KRAS mutation status and response to chemotherapy and survival were assessed.

Results: We identified 80 patients with metastatic or recurrent NSCLC and a KRAS activating mutation, and we compared these patients to 70 patients who were pan negative (no detectable mutation by the SNaPshot assay and ALK negative). Patients with KRAS-mutant advanced NSCLC demonstrated a significantly shorter progression-free survival in response to first line chemotherapy (4.5 months versus 5.7 months, p=0.008) compared to pan-mutation negative patients. Overall survival was also significantly shorter in patients with KRAS-mutant advanced NSCLC compared to patients without KRAS activating mutations (8.8 months versus 13.5 months, p=0.038).

Conclusions: Within this single institution retrospective analysis, patients with advanced NSCLC and a KRAS activating mutation exhibited inferior responses to cytotoxic chemotherapy and decreased survival compared to patients with advanced NSCLC and no KRAS mutation.