Clinical outcome of KRAS-mutated advanced non-small cell lung cancer (NSCLC) patients (pts): A mono-institutional analysis.

Abstract

7580 Background: In the present analysis we evaluated the clinical outcome of KRAS mutated advanced non-small cell lung cancer (NSCLC) patients (pts) treated at a single Institution from April 2007 to December 2010. Methods: KRAS mutational status was assessed on tumor tissue collected at the time of first diagnosis (either primary or metastatic). KRAS (exons 2 and 3) gene was amplified by nested PCR and sequenced in both sense and antisense direction using 3500 Genetic Analyzer. Retrospective chart review was approved by the local Ethics Committee. Results: 64 pts with an identified KRAS mutation were evaluable for the analysis. The majority of them (87.5%) had a good performance status (ECOG 0), while 82.5% were former or current smokers. All pts except for one who was treated with single-agent gemcitabine, received a platinum-based doublet mainly including either gemcitabine (56,5%) or pemetrexed (25%). Overall, 82% of pts received at least two lines of chemotherapy. Three types of KRAS mutations were identified, the most common being codon 12 (78.1%) mutation, followed by codon 13 (12.5%) and codon 61 (9.4%) mutations, respectively. Of the 52 (81,2%) who were evaluable for response 2 complete responses (3,8%), 21 partial responses (40,4%), 13 disease stabilizations (25%) and 16 progressive diseases (30,8%) were observed. Median overall survival (OS) from the beginning of treatment was 39 months, with no statistically significant differences according to the type of K-RAS mutation (p< 0,2). Median OS and first-line PFS were significantly higher in responders versus non-responders (55.4 months versus 24.8 months for OS and 11.2 months versus 4.8 months for first-line PFS, p<0.009). Conclusions: KRAS mutated NSCLC pts do not represent a population with homogeneous clinical characteristics. Response to treatment seems to predict benefit from first-line chemotherapy in terms of OS and first-line PFS. The excellent OS rate observed in the whole group might be the result of a population highly selected for good clinical prognostic factors. Prospective studies of KRAS mutations and sensitivity to chemotherapy are warranted.