Markers of proliferation, apoptosis in breast cancer similar between vandetanib, placebo

A pilot study of preoperative vandetanib has found no statistically significant differences on prespecified markers when compared with placebo.

Ten patients with invasive breast cancer were randomized to receive the tyrosine kinase inhibitor vandetanib 300 mg or placebo daily for 2 weeks before operative resection from January 2014 to June 2017. Pre- and post-treatment specimens were analysed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by RET expression by immunohistochemistry.

No statistically significant difference was seen in ERK activation compared with placebo (p=0.45), but ERK activation decreased by 74 percent compared with pretreatment biopsy with vandetanib treatment (p=0.005) without a significant reduction in the placebo group (–29 percent; p=0.55).

Mean change in Ki-67 after vandetanib treatment was 0.3 percent compared with 2.0 percent in placebo-treated patients (p=0.72). Mean change in TUNEL was 0.48 and 1.02 apoptotic nuclei per HPF in the vandetanib and placebo arms, respectively (p=0.32).

In patients who received vandetanib, Ki-67 decreased by 0.3 percent in RET-positive tumours compared with a 1.0-percent increase in RET-negative tumours (p=0.43); TUNEL increased by 0.77 in RET-positive tumours and by 0.2 in RET-negative tumours (p=0.21).

“In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in RET-expressing tumours,” the authors said.

“Preclinical data supports antitumour activity of tyrosine kinase inhibitor vandetanib with RET as the therapeutic target in breast cancer,” they noted.