A prospective phase II trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients (p) with mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR)

Abstract

7020 Background: The EGFR TK inhibitor erlotinib is a standard treatment in previously treated NSCLC p. Recently, EGFR gene mutations have been reported to be a predictor of efficacy of this and related compounds. This phase II trial evaluated the efficacy and safety of erlotinib in untreated p with advanced NSCLC and mutated EGFR. Methods: Eligibility criteria included stage IIIB-IV chemotherapy-naive p with confirmed NSCLC and mutated EGFR, PS 0–2, age ≥ 18 years, adequate organ functions, measurable disease and written informed consent. DNA was extracted by laser capture microdissection. Exon 19 deletions were examined by Genscan and the L858R and T790M mutations with a TaqMan assay. Mutations were confirmed by sequencing. Erlotinib was given orally at 150 mg per day. Results: From March to December 2005, 37 (12.5%) of 297 tumors screened were found to have mutations in the TK domain of the EGFR gene (25 deletions; 11 L858R; no T790M). Median age: 68 years; 12 males, 25 females; histology: 28 adenocarcinoma, 4 BAC, 4 large cell carcinoma; 9 smokers. Response has been evaluated in 21 p so far: complete response, 6 p; partial response, 13 p; progressive disease, 2 p; overall response rate, 90% (95% CI:70%-90%). Responses occurred in 100% of tumors with exon 19 deletions and in 75% of those with L858R. All responses are ongoing (up to ≥8 months) and all but one p are still alive. Toxicity profile was predictable (mild to moderate rash, diarrhea, asthenia and emesis). No drug related severe adverse events occurred. Conclusions: Single-agent erlotinib produces a high response rate in previously untreated p with advanced NSCLC and mutated EGFR. In-frame deletions in exon 19 seem particularly predictive for response in this setting. [Table: see text]