Soluble epidermal growth factor receptor (EGFR) and HER-2 monitoring in a Phase II combination of gefitinib (ZD1839) and docetaxel for non-small-cell lung cancer (NSCLC)

Abstract

7090 Background: We previously reported the preliminary activity and tolerability of the combination of the EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) and docetaxel in patients with advanced NSCLC who have failed (Group A) or are unsuitable (Group B) for platinum-based chemotherapy (Proc Am Soc Clin Oncol 2003; 22: 661, abs 2659). In this analysis, we aimed to determine the predictive biologic factors of response to this combination by measuring the soluble EGFR and HER-2 levels before initiation of treatment. Methods: Daily oral gefitinib (250 mg/day) was combined with docetaxel (75 mg/m2) every 3 weeks starting on day 1. Updated clinical analysis is as follows: 43 patients were included between 07/2002 and 10/2003; male/female: 28/15; median (range) age: 57 (21–84) years; WHO PS 0/1/2: 17/22/4; Group A: 30 patients, Group B: 13 patients; 37 stage IV, 6 stage IIIb, median (range) number of involved organs: 2 (1–4). Results: To date, efficacy data according to RECIST are available for 37 patients; 8 partial response (PR) and 15 stable disease were documented (all PR were in Group A). Biologic monitoring by ELISA test (soluble active EGFR and HER-2) was done before and during treatment. There was no statistically significant difference between responding and non-responding patients at baseline for mean soluble EGFR levels (64 ± 62 vs 118 ± 217 pmol/mL, p=0.03) and HER-2 (1.278 ± 0.59 vs 1.520 ± 0.35 pmol/mL, p=0.1). However, responding patients exhibited a stable level of soluble EGFR during therapy while this level increased significantly in non-responders (p=0.03 at Cycle 3). Median progression-free and overall survival, as well as EGFR and HER-2 expression analyzed by immunohistochemistry on primitive tumor cells, will be presented at the meeting. Conclusion: Initial soluble EGFR and HER-2 determinations do not predict response to gefitinib-docetaxel combination in this cohort. 'Iressa' is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca