Evaluation of the prognostic/predictive role of tumor EGFR and KRAS mutations in Greek metastatic non-small cell lung cancer patients treated with first-line chemotherapy.

Abstract

e19048 Background: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC). Little is known about the prognostic/predictive role of KRAS in advanced NSCLC, with conflicting results among small studies. Recent evidence showed that KRAS mutations could predict for worse outcome in patients treated with platinum-based adjuvant chemotherapy. Methods: KRAS and EGFR genotypes were evaluated in 414 NSCLC patients with available clinical data, diagnosed from March 2000 to December 2012 (tissue blocks from the HeCOG tumor repository). KRAS and EGFR mutations were associated with clinicopathological parameters (mutated vs. wild-type). Outcome comparisons were performed in 214 metastatic patients with treatment data available, following 1st-line chemotherapy without tyrosine kinase inhibitors. Results: The majority of the patients were male (80%), current smokers (53%), with adenocarcinoma (AC) histology (65%). EGFR mutations were found in 10% and KRAS mutations in 17% of all histological types, while in AC they were 14% and 21%, respectively. Most EGFR mutations were classical (79%), while most common KRAS mutations were p.G12C (39%), p.G12D (30%) and p.G12V (15%). Two tumors had concurrent EGFR and KRAS mutations. EGFR mutations were significantly associated with female gender, AC histology and non-smoking status, as previously described. KRAS mutations were associated with AC histology and younger age (<60). At a median follow-up of 31 months, EGFR status did not show any significant associations with OS or PFS, while KRAS mutations were prognostic for worse OS compared to KRAS and EGFR wild-type tumors (HR=1.67, CI=1.08-2.59, p=0.021). This effect was also significant (p=0.022) in the presence of treatment type, with platinum-based therapy being a positive prognostic factor for OS (HR=0.62, CI=0.4-0.92, p=0.019). The association of KRAS mutations with PFS was not significant. Conclusions: EGFR and KRAS genotype incidences are presented for the first time for Greek metastatic NSCLC patients. In this setting, the presence of KRAS mutations significantly increases and platinum 1st-line treatment decreases the risk of death.