Association of an aurora kinase a (AURKA) gene polymorphism with progression-free survival in patients with advanced urothelial carcinoma treated with the selective aurora kinase a inhibitor alisertib.

Background and purpose Salvage therapies for urothelial carcinoma are needed. A single-arm trial in patients with advanced or metastatic urothelial carcinoma refractive to other therapies found that alisertib, a selective inhibitor of aurora kinase A, maintained stable disease in a few cases, despite a low objective response rate. To better understand why some patients benefited from alisertib, we genotyped the 22 patients of this pilot trial for two single nucleotide polymorphisms (rs2273535 and rs1047972) in AURKA, the gene encoding aurora kinase A, and looked for associations with survival and treatment response. Results Carrier status for the minor allele of rs2273535 (T91A, p. F31I) was a favorable prognostic factor for progression-free survival (HR = 0.18; 95% CI, 0.039-0.81; P = 0.026) but not for overall survival (HR = 0.88; 95% CI, 0.26-2.9; P = 0.83). These results were confirmed in multivariable analyses, adjusting for sex, age and hemoglobin, for both progression-free survival (HR = 0.11; 95% CI, 0.018-0.69; P = 0.018) and overall survival. No association was found between rs1047972 and survival. Moreover, neither SNP was associated with treatment response. Conclusion In patients who received alisertib for advanced or metastatic urothelial carcinoma, longer progression-free survival was observed in carriers of the minor allele A of rs2273535 in AURKA than in patients who were homozygous for the major allele T. This finding, based on a small pilot trial, warrants further investigation.