Analysis of the prognostic role of plasmatic K-ras mutations in advanced non-small cell lung cancer (NSCLC) patients

Abstract

18009 Background: Qualitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of K-ras mutations at codon 12 and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. K-ras mutational status was determined by a method based in allelic discrimination with RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Here we present the results of the analysis of K-ras mutations in the plasma of 165 samples. 17 patients presented K-ras mutations (10.3%), being codon 12 TGT in 16 patients and GTT in 1 case. Plasmatic mutations were found either in patients presenting squamous cell carcinoma (n=3) and in patients with adenocarcinoma (14). Patients with K-ras mutations in plasma had a median time to progression (TTP) of 2.3 months (m) [0.5- 4.6] while for wild type K-ras was 4.1 m [3.3–4.8], (p=0.9). Overall Survival (OS) in K-ras mutated patients was 10.1 m [4.1–15.8] and in wild type K-ras was 9.0 m [6.9–11.1], (p=0.6). Conclusions: In advanced NSCLC, there were no significant differences between patients with K-ras mutations and those with wild-type genotype with respect to baseline characteristics, response rates, TTP, or OS. Data from the rest of the cohort will be presented at the meeting. No significant financial relationships to disclose.