The New Drug Alisertib Performs Well in a Phase I Trial

“In a phase II study reported in The Lancet Oncology, Melichar et al found that the oral aurora kinase A inhibitor alisertib was active in solid tumors, particularly breast cancer and small cell lung cancer. Aurora kinases play central roles in mitosis. Inhibition of aurora kinase A, which is overexpressed/amplified in several tumor types and associated with poorer outcome, results in abnormal spindle formation, mitotic defects, and cell death.

“In the five-arm study, patients with disease that had relapsed or was refractory to chemotherapy and who had received up to two previous cytotoxic regimens (up to four for breast cancer), not including adjuvant or neoadjuvant treatment, were enrolled from 40 centers in the Czech Republic, France, Poland, and the United States between February 2010 and May 2013. Patients received alisertib at 50 mg twice daily for 7 days followed by 14 days off in 21-day cycles. Objective response was the primary endpoint.

“Among response-assessable patients, objective response (all partial responses) was observed in 9 (18%, 95% confidence interval [CI] = 9%–32%) of 49 women with breast cancer, 10 (21%, 95% CI = 10%–35%) of 48 patients with small cell lung cancer, 1 (4%, 95% CI = 0%–22%) of 23 with non–small cell lung cancer, 4 (9%, 95% CI = 2%–21%) of 45 with head and neck squamous cell carcinoma, and 4 (9%, 95% CI = 2%-20%) of 47 with gastroesophageal adenocarcinoma.”