Interim safety analysis of a phase II study of erlotinib (E) alone or combined with fulvestrant (F) in previously treated patients with advanced non-small cell lung cancer (NSCLC)

Abstract

19091 Background: Laboratory work shows that NSCLC cells and primary tumors express estrogen receptors (ER) that contribute to growth promotion (Stabile et al. Cancer Res. 62: 2141, 2002; Weinberg et al. Cancer Res. 65: 11287, 2005). Preclinical evaluation demonstrates considerable interaction between the ER and EGFR pathways with additive effects on NSCLC cell lines when both pathways are inhibited. We designed a phase II study to evaluate whether inhibition of ER with the ER downregulator, fulvestrant (F), could add to the anti-tumor efficacy of EGFR inhibition with erlotinib (E). The study design includes an interim safety analysis after 5 patients receive E+F, as no safety data with this combination was available at study onset. Methods: Men and women (pre- and post-menopausal) with advanced NSCLC and at least one prior chemotherapy regimen are randomly assigned in a 2:1 ratio to receive E (150 mg PO qd) with or without high-dose F (500 mg IM q2wk x 3, then q4wk). The primary endpoint is response rate at 2 months. Secondary endpoints include correlation between response and ERα, ERβ, EGF/HER-1 receptor and HER-2/neu expression. Results: 14 patients have been enrolled, 9 assigned to E+F (one withdrew prior to therapy) and 5 to E. On the E+F arm, 1 patient withdrew at d18 for a grade 3 rash. On the E arm, 1 patient had visible progression of a chest wall mass at d28. All remaining patients completed at least 8 weeks of therapy. One patient receiving E+F developed a GI bleed complicated by MI at d95. No other grade 3 or 4 toxicities were seen. The most common toxicity was rash, with little difference in overall toxicity between the two arms. Conclusions: In this group of previously treated men and women with NSCLC, the tolerability of E+F is acceptable. Therefore, the Data Safety and Monitoring Board allowed the study to continue. Per protocol, we can now expand the study beyond UCLA, and we plan to involve the TORI research network to help complete accrual and evaluate for efficacy of the combination in men and women with advanced NSCLC. [Supported by NIH Lung Cancer SPORE P50-CA90388 and P50-CA90440, AstraZeneca, Genentech, Stiles Program] Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology, Genentech™ BioOncology