GEFITINIB FOR BREAST CANCER?

NEW YORK (Reuters Health) Mar 25 - Adding the epidermal growth factor receptor (EGFR) inhibitor gefitinib to anastrozole improves progression-free survival in postmenopausal women with hormone receptor-positive metastatic breast cancer, new research shows.

In the March 15th issue of Clinical Cancer Research, the researchers note that gefitinib inhibited HER2-overexpressing breast cancer cells in preclinical studies.

In a phase II trial, Dr. Massimo Cristofanilli from The University of Texas M. D. Anderson Cancer Center, Houston, and colleagues compared the combination regimen with anastrozole plus placebo. They randomized 93 postmenopausal breast cancer patients with hormone receptor-positive metastatic disease: 43 to the intervention group and 50 to the control group.

Women who received anastrozole plus gefitinib had longer median progression-free survival (14.7 vs 8.4 months) and higher clinical benefit rates (49% vs 34%).

The objective response rate was numerically lower with anastrozole plus gefitinib (2%) than with anastrozole plus placebo (12%), but the difference was not statistically significant.

In a post hoc analysis, a history of endocrine treatment had an adverse effect on survival in the gefitinib/anastrozole group. Among the women who received the two-drug regimen, median progression-free survival was 11.2 months with previous endocrine therapy, compared to 20.2 months without it.

Baseline biomarker levels, serum levels of HER2, and serum EGFR levels had no impact on progression-free survival or clinical benefit rates.

Adverse events were mostly mild, although the incidence of treatment-related adverse events was higher for anastrozole-gefitinib (79%) than for anastrozole-placebo (38%). Serious adverse events occurred with similar frequency in the anastrozole plus gefitinib (6/43, 14%) and anastrozole plus placebo (8/50, 16%) arms of the study.

"This study showed that anastrozole in combination with gefitinib was associated with a marked advantage in progression-free survival and a numerical improvement in clinical benefit rate compared with anastrozole plus placebo, in spite of smaller than planned patient numbers, and that the combination was tolerated in postmenopausal women with hormone receptor-positive metastatic breast cancer," the investigators conclude.

Clin Cancer Res 2010;16:1904-1914.