P2.15-016 Clinical Significance of Topoisomerase-II Expression in Patients with Relapsed HGNEC of the Lung Treated with Amrubicin

Amrubicin (AMR) monotherapy is one of treatment options in patients with relapsed high grade neuroendocrine carcinoma (HGNEC) of the lung. Although topoisomerase-II (Topo-II), a target of AMR, has been reported to be a predictive or prognostic marker for chemosensitivity and clinical outcomes in various types of malignancies, its role remains unknown in this population. Eighty-four patients with relapsed HGNEC (consisting of small cell lung cancer [SCLC] and large cell neuroendocrine carcinoma [LCNEC]) who received AMR monotherapy between 2003 and 2015 were enrolled into this study. We retrospectively collected clinical data including histological type, anti-tumor effect, and survival data from medical records. The expression levels of Topo-II were examined by immunohistochemical staining in tumor specimens obtained from surgical resection or biopsy. The majority of enrolled patients were men (89%) and had a histological type of SCLC (92%) with a median age of 70 years (range, 49-83 years). Twenty-three percent of patients had poor performance status of 2 to 4. Sixteen percent of patients exhibited Topo-II overexpression in the tumors. The overall response rates in patients with high and low expression of Topo-II were 38.5% and 25.7%, respectively (p = 0.34). In multivariate analysis, patients with high expression of Topo-II had significantly longer progression-free survival (Hazard Ratio [HR] 0.39, p <0.01) and overall survival (HR 0.48, p = 0.04). Our findings suggest that Topo-II expression is associated with clinical outcomes in patients with relapsed HGNEC receiving AMR monotherapy.