AURORA KINASE A INHIBITORS-EFFECTIVE IN BREAST CANCER AND SCLC

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.

Study Details

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.

Response Rates

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.

Toxicity

Adverse events were similar across tumor types. The most common drug-related grade 3 or 4 adverse events were neutropenia (43%), leukopenia (21%), and anemia (10%). Serious adverse events were reported in 43% of patients and were considered drug-related in 18%, with the most common drug-related events being febrile neutropenia (4%) and anemia (4%). Adverse events led to dose reduction in 28% of patients and to discontinuation of treatment in 10%.

The investigators concluded: “These data support further clinical assessment of alisertib in patients with solid tumours, particularly those with breast cancer and small-cell lung cancer.”

Bohuslav Melichar, MD, of Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic, is the corresponding author for The Lancet Oncology article.

The study was funded by Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. For full disclosures of the study authors, visit www.thelancet.com.