Predicting the Role of DNA Polymerase ß Alone or with KRAS Mutations in Advanced NSCLC Patients Receiving Platinum-Based Chemotherapy.

ABSTRACT

Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase ß expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase ß expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR) 1.37, 95% confidence interval (95% CI) 0.70-2.27). Negative DNA polymerase ß staining identified a subgroup with worse OS than patients expressing the protein (HR 1.43, 95% CI 0.57-3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase ß staining (HR 1.67, 95% CI 0.52-5.56). DNA polymerase ß did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase ß, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase ß further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used.