A phase II multicenter, double-blind, randomized trial to compare anastrozole plus gefinitib with anastrozole plus placebo in postmenopausal women with hormone receptor-positive (HR+) metastatic breast cancer (MBC)

Abstract

1012 Background: Preclinical data provide evidence that suggests crosstalk between growth factor receptor pathways and the estrogen receptor (ER). Inhibition of both epidermal growth factor receptor and ER signalling may thus be a potential intervention to overcome hormonal resistance. We performed a phase II study to evaluate efficacy and tolerability of anastrozole (Arimidex) plus gefitinib (IRESSA) [A+G] vs. anastrozole plus placebo [A+P] for treatment of newly diagnosed HR+ MBC in postmenopausal women. Methods: A total of 94 women with newly diagnosed HR+ MBC were randomized (1:1) (one woman died prior to treatment) to receive anastrozole 1 mg/day and either gefitinib 250 mg/day or placebo (50 to A+P; 43 to A+G). Hormone receptor status was reviewed at a central laboratory. Primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate (RECIST criteria) and clinical benefit rate (CBR; defined as objective response or stable disease ≥24 weeks), overall survival, safety and tolerability. Enrollment was stopped early due to slow recruitment and hence limited statistical analyses were performed. Results: A marked PFS advantage was seen for A+G over A+P (hazard ratio [A+G:A+P] 0.55, 95% CI 0.32–0.94, median 14.5 m vs 8.2 m). A numerical advantage in CBR was seen for A+G vs. A+P. Safety and tolerability profiles showed no unexpected findings. Treatment-related adverse events (AE) were seen in 79% of patients in the A+G arm vs. 38% in the A+P arm and were mostly mild. Two patients in the A+G arm and 1 patient in the A+P arm experienced an AE with outcome of death; none were considered treatment related. Conclusions: Anastrozole plus gefitinib was well tolerated and associated with a marked advantage in PFS vs. anastrozole plus placebo in postmenopausal women with newly diagnosed HR+ MBC. The data suggests the need for further investigation of this combination. Anastrozole plus gefitinib (n = 43) Anastrozole plus placebo (n = 50) Complete response (CR), n (%) 1 (2) 1 (2) Partial response (PR), n (%) 0 (0) 5 (10) Stable disease ≥ 24 weeks (SD), n (%) 20 (47) 11 (22) Clinical benefit rate (CR+PR+SD), n (%) 21 (49) 17 (34) 95% CI for clinical benefit rate 33–65 21–49 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca