Phase II study of gefitinib treatment in advanced thymic malignancies.

7068 Background: Thymomas and thymic carcinomas are rare epithelial tumors arising from the thymus gland. Malignant thymic tumors have shown to express the epidermal growth factor receptor (EGFR). This study evaluates the activity of gefitinib, an EGFR tyrosine kinase inhibitor, in patients (pts) with advanced thymoma/thymic carcinoma.,Primary objective was to determine the objective response rate of gefitinib in previously treated pts, with advanced thymoma or thymic carcinoma. Secondary objectives were to determine duration of remission and toxicity.,Twenty-six (female = 15, male = 11) previously treated pts with metastatic thymoma (n = 19) or thymic carcinoma (n = 7), with ECOG performance status of 0 or 1, were enrolled from January 21, 2003 to June 14, 2004. Nineteen pts had prior radiation therapy. Median number of prior systemic therapies was 2.5 (range, 0 - 6). Pts received gefitinib orally at 250 mg daily. Each treatment cycle was 28 days. Pts obtaining a complete remission (CR), partial remission (PR), or stable disease (SD) for 2 treatment cycles, continued therapy until progression, or a maximum of 8 cycles of treatment. Genomic DNA was extracted from 5 paraffin-embedded tumor blocks and sequenced for mutations (EGFR exons 18 to 21, KRAS2 exon 2).,All 26 pts were evaluated for response and toxicity. There were 0 CRs, 1 PR (response duration = 5 months), and 14 SDs. Six pts had SD for > 4 months. Grade 3/4 adverse events noted were: dyspnea (grade 4, n = 1; grade 3, n = 2), fatigue (grade 4, n = 1), anemia/thrombocytopenia (grade 4, n = 1), and myocardial infarction (n = 1). After completing 3 cycles, the patient with a PR developed presumed gefitinib-induced Grade 2 pneumonitis, which resolved following steroids and discontinuation of treatment. Median time to progression (TTP) was 4 months (range, 1 - 17+). Twenty-five of the 26 pts remain alive. None of the 5 pts (including 1 PR), analyzed by DNA sequencing, had evidence of EGFR or KRAS mutations.,With limited number of tumors analyzed in this study, EGFR mutations do not appear to be common in thymic malignancies. Gefitinib is well tolerated, with minimal activity in this heavily pretreated population. (Supported in part by AstraZeneca.) No significant financial relationships to disclose.