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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

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Summary

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.

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Acknowledgements

Valerie Matarese provided scientific editing.

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Authors and Affiliations

  1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Andrea Necchi, Daniele Raggi & Patrizia Giannatempo

  2. Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G.A. Amadeo 42, I-20133, Milan, Italy

    Giulia Pintarelli & Francesca Colombo

Authors
  1. Andrea Necchi
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  2. Giulia Pintarelli
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  3. Daniele Raggi
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  4. Patrizia Giannatempo
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  5. Francesca Colombo
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Corresponding author

Correspondence to Francesca Colombo.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The study was partially supported by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The company had no role in the design or conduction of the study, in the collection, analysis or interpretation of the data, or in the preparation, review and approval of the manuscript.

Ethical approval

All procedures performed in the present study, involving human participants, were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later revisions and amendments.

Informed consent

Informed consent was obtained from all participants included in the study.

Additional information

Andrea Necchi and Giulia Pintarelli contributed equally to the study.

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Necchi, A., Pintarelli, G., Raggi, D. et al. 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. Invest New Drugs 35, 524–528 (2017). https://doi.org/10.1007/s10637-017-0440-5

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  • DOI: https://doi.org/10.1007/s10637-017-0440-5

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