P1-31-1 - Transformation to Small-Cell Lung Cancer Following Treatment with Vandetanib in a Patient with Lung Adenocarcinoma

Abstract

We report the case of a 79-year-old woman harboring EGFR-activating mutation with relapsed lung adenocarcinoma treated with Vandetanib, an oral inhibitor of VEGFR, EGFR, and RET signaling. She presented with cough and dyspnea in January 2006. Transbronchial lung biopsy revealed an adenocarcinoma, and the patient was diagnosed with lung cancer (cT4N0M0, stage IIIB, 6th edition). EGFR analysis revealed an exon 19 deletion. After three cycles of first-line chemotherapy with carboplatin and paclitaxel, she received docetaxel (60 mg/m2 in a 1-h intravenous infusion every 3 weeks; six cycles) in combination with Vandetanib (100 mg/day orally) until disease progression (ZODIAC). Her best tumor response was partial response and progression free survival is 4.8 years. After progression, administration of some new agents did not lead to radiologic improvement. Then, histological examination of a secondary biopsy was performed and specimen revealed typical small-cell lung cancer (SCLC) retaining the same EGFR mutation. Immunochemistry staining demonstrated positive for Thyroid nuclear factor 1 (TTF-1), Synaptophysin, Chromogranin A, and CD56, but negative for P40. Tumor markers, ProGRP and NSE, were elevated. She subsequently underwent combination chemotherapy with etoposide and carboplatin, and a chest CT after two cycles revealed a partial response. Transformation to SCLC is a mechanism for acquired resistance to EGFR-TKI therapy. Secondary biopsy is important for evaluation of genetic and histological changes and selection of appropriate treatment. This is a first report in transformation to SCLC after the Vandetanib use.