Clinical and biological effects of gefitinib in EGFR FISH positive/phospho-akt positive or never smoker non-small cell lung cancer (NSCLC): Preliminary results of the ONCOBELL trial

Abstract

7023 Background: Effectiveness of gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), in never smokers and/or EGFR FISH positive NSCLC patients has been evaluated only in retrospective studies and few data exist on the biological effects of gefitinib therapy in tumor samples. Methods: The ONCOBELL trial is a multicenter prospective phase II study designed to include 39 patients EGFR FISH positive/phospho-Akt (p-AKT) positive and/or never smokers with advanced or metastatic NSCLC. Gefitinib is given at the daily dose of 250 mg. When feasible, primary tumor biopsy was repeated immediately before therapy, during therapy and at progression. Specimens were evaluated for EGFR and HER2 gene copy number by FISH, EGFR gene mutation by DNA sequencing, and EGFR and p-AKT protein expression by immunohistochemistry. Results: Data from the first 28 enrolled patients are available: median age was 60 years (range, 43–80); male/female: 7/21; stage IIIB/IV: 2/26; ECOG PS 0/1/2: 18/6/4; 25 patients had a diagnosis of adenocarcinoma and/or bronchioloalveolar carcinoma; 13 patients had brain metastases, and in 10 cases gefitinib was offered as first-line therapy. Twenty-four patients were never smokers and 19 were EGFR FISH positive. Overall response rate was 54%, including 1 complete and 14 partial responses. Median time to progression was 6.45 months, and median survival was not reached. Response to therapy was not influenced by previous therapies or presence of brain metastases. Toxicity was mild, and consisted in grade 1–2 skin rash (68%) and diarrhea (57%). One patient developed grade 3 diarrhea and another patient was hospitalized for acute interstitial lung disease. In patients exposed to previous chemotherapy, no difference in EGFR or HER2 FISH results were observed in specimens collected at the time of original diagnosis compared to specimens collected immediately before gefitinib therapy. In 14 cases primary tumor biopsy was repeated during gefitinib therapy. Conclusions: These preliminary data indicate that gefitinib is highly effective in patients with trial characteristics. Clinical and biological data for the entire cohort will be available in June 2006. No significant financial relationships to disclose.