gms | German Medical Science

Introduction: Inhibition of epidermal growth factor receptor (EGFR) activity is a new concept for treatment of patients with non small cell lung cancer (NSCLC). Second and third line treatment with Gefitinib (Iressa™), a small molecule inhibitor of EGFR, has an objective response rate of 12 - 18%. We present sngle center results of the treatment of patients within an expanded access program and data of the mutational analysis of EGFR.

Methods: Complete follow-up is available for 68 patients with NSCLC, 24 female and 44 male, median age 61 years. 80% were smokers with a median of 40 pack-years. Histology was adenocarcinoma in 80% (bronchioloalveolar carcinoma (BAC) or BAC features in 12%), squamous cell carcinoma in 12% and others in 8% of the patients. 91% had stage IV disease and 50% had a Karnofsky score of at least 80. 76% had been treated with chemotherapy, 58% platinum-based. Patients were treated with oral Gefitinib, 250 mg/d. EGFR mutations were analyzed by DNA sequencing of exons 18, 19 and 21.

Results: Gefitinib treatment resulted in objective response in 35% of the patients (10% partial remission and 25% stable disease). Another 13% of the patients experienced subjective improvement without objective response for an overall clinical benefit rate of 48%. The median time to objective response was 44 days (16 - 92 days). 67% of the patients experienced adverse events, 51% CTC grade 1, 6% grade 2, 5% grade 3 and 5% grade 4. The most common adverse events were skin reactions (45%) and diarrhea (23%). Three of 22 completely sequenced tumor biopsies contained mutations. There were 2 heterozygous in-frame deletions at position LREA in exon 19 and one substitution of arginine for leucine at position 858 (L858R), both known activating mutations within the coding region of the EGFR tyrosine kinase. Two male patients with EGFR mutations had excellent subjective and objective response to Gefitinib for 12 and 15 months. One responding female patient is currently being treated for 10 months. All 3 patients were smokers. Two had BAC and one adenocarcinoma without BAC features. 1 of 10 patients without detectable mutations experienced improvement of symptoms and stable disease.

Conclusions: This study confirms significant activity of Gefitinib in NSCLC. Patients with activating EGFR mutations had excellent response to treatment. Sequencing data for a total of 30 patients will be demonstrated and compared to EGFR immunohistology and EGFR FISH.