EGFR mutations and gefitinib sensitivity in patients with metastatic non-squamous non-small cell lung cancer

Abstract

19075 Background: Probability of clinical benefit from EGFR tyrosine kinase inhibitors in previously treated NSCLC pts is strongly associated with the presence of EGFR mutation. However, the experience of gefitinib application as the first-line therapy in mutation-positive pts remains limited. Methods: EGFR analysis included the detection of the exon 19 deletions and 858TG mutation in paraffin embedded tumor specimens. Chemo-naïve mutation-positive pts received gefitinib (250 mg/d p.o.) until disease progression or unacceptable toxicity. The primary outcome was the response rate (RR) according to RECIST criteria. Results: tumor specimens from 52 pts with advanced non-squamous NSCLC were enrolled (median age - 58,6 years; adenocarcinomas - 82%, BAC - 8%, other - 10%). EGFR mutations were found in 11 of 52 pts (21%) with adenocarcinomas only. 9 mutations were exon 19 deletions and 2 - codon 858 substitutions. 6 chemo-naïve pts with stage IV adenocarcinomas were selected for treatment with gefitinib (median age: 62,6 years; M/F - 4/2; ECOG PS 1/2/3 - 2/3/1; exon 19 deletions - 6/6). Adverse events were mainly grade 1–2 rash (4/6) and grade 3 rash in 2 pts. The overall RR was 67% (PR 67% and CR 0%) (4/6) with disease stabilization in 33% (2/6). Median time to disease progression was 8.0 months (2.5–12.5 months). Conclusions: 1st-line gefitinib therapy in EGFR mutation-positive NSCLC pts is feasible, well tolerated, and yields a substantial RR and PFS. No significant financial relationships to disclose.