Alisertib, an investigational, oral, selective inhibitor of aurora kinase A, showed antitumor activity in preclinical in vivo small cell lung cancer (SCLC) models and was synergistic with paclitaxel, according to results from a randomized phase 2 study presented at the International Association for the Study of Lung Cancer (IASLC) 17th Annual World Conference on Lung Cancer in Austria.1

Patients who were 18 years or older with SCLC who had relapsed less than 180 days after standard first-line platinum-based chemotherapy were randomized 1:1 to either alisertib plus paclitaxel (Arm A), or matched placebo paclitaxel (Arm B).

Patients were stratified using an interactive voice response system (IVRS) by type of relapse post-frontline platinum (sensitive vs resistant/refractory) and presence or absence of brain metastases at baseline. The study’s primary endpoint was progression-free survival (PFS) per stratified log-rank test. Quality of Life (QOL) outcomes were also assessed.

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In total, 178 patients with median age of 62 years were randomized 1:1 to either study arm. The analysis of PFS using IVRS stratification favored Arm A, as did the analysis per corrected stratification factors. Mean QOL scores were similar between arms.

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The study found favorable PFS in the alisertib + paclitaxel arm compared to placebo + paclitaxel with both initial and updated IVRS stratification. Researchers observed a similarly favorable trend for overall survival and objective response rate, although the trend was not statistically significant.

Comparable changes in QOL scores were observed from baseline in both arms. The alisertib + paclitaxel arm showed higher rates of adverse events and discontinuation due to them. 


  1. Owonikoko TK, Nackaerts K, Csoszi T, et al. Randomized phase 2 study: alisertib (MLN8237) or placebo + paclitaxel as second-line therapy for small-cell lung cancer (SCLC). Paper presented at: International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria.