Combination therapy with gefitinib and fulvestrant (G/F) for women with non-small cell lung cancer (NSCLC)

Abstract

7224 Background: Estrogen receptors (ERs) have been detected in NSCLC specimens. Fulvestrant has blocked estradiol-stimulated tumor growth in NSCLC cell lines. Preclinical data show an inverse cross-talk between the EGFR and ER pathways. Objectives: Determine safety and efficacy of G/F and correlate with markers of ER and EGFR pathways. Methods: Post-menopausal women with advanced NSCLC received gefitinib 250 po mg daily and fulvestrant 250 mg IM monthly, every 28 days. Results: Accrual goal is 22 pts; 15 have enrolled to date. Median age is 72 yrs. 8 pts had adenocarcinoma, 3 squamous cell, 3 NSCLC-NOS, and 1 bronchoalveolar carcinoma. 5 pts never smoked; 9 were former smokers. Prior lines of chemotherapy received: ≥2 (6 pts), 1 (5 pts), 0 (4 pts). PS: 0 (7 pts), 1 (6 pts), 2 (2 pts). Gr 3/4 treatment-related toxicities: Gr 4 dyspnea (1 pt). No unexpected toxicities have been seen. 11 pts are evaluable for response: 2 confirmed PRs (1 adenocarcinoma and 1 NSCLC-NOS), both in never smokers. Median number of cycles of treatment, PFS, and OS are 5.29 cycles, 21 wks, and 28+ wks (not yet reached; range 7–38+). 6 pts have stable disease [SD] (1 current smoker, 4 former smokers, 1 never smoker); the median duration of SD is 21 wks. There was no correlation between total ER or amount of nuclear ER staining and response to treatment or histology in 8 tumors examined. 1 patient receiving 2nd-line treatment had a heterozygous point mutation (G2591A) in EGFR exon 21 and SD for 21 wks; neither pt with PR had sufficient tumor for mutation analysis. None of the 6 tumors analyzed displayed EGFR gene amplification. Genotyping for MDR-1 and CYP3A4*1B was performed in 11 tumors; variants did not correlate with toxicity or response. Conclusions: G/F in post-menopausal women with NSCLC is well-tolerated and demonstrates disease activity. Correlative studies indicate there is no relation between amount of ERα, ERβ or EGFR expression in the tumor and response to treatment. 5 of the 6 pts with SD were active or former smokers. 1 pt with an EGFR mutation had prolonged SD, but no PR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, EMD, Genentech, Millenium, Taiho AstraZeneca, GlaxoSmithKline, Lilly Oncology, Taiho AstraZeneca, CellGate, GlaxoSmithKline, Lilly Oncology