Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer

Breast Cancer Research and Treatment
Tufia HaddadJames N Ingle

Abstract

In estrogen receptor-positive (ER+) breast cancer models, activation of Aurora A kinase (AURKA) is associated with downregulation of ERα expression and resistance to endocrine therapy. Alisertib is an oral selective inhibitor of AURKA. The primary objectives of this phase I trial were to determine the recommended phase II dose (RP2D) and evaluate the toxicities and clinical activity of alisertib combined with fulvestrant in patients with ER+ metastatic breast cancer (MBC). In this standard 3 + 3 dose-escalation phase I study, postmenopausal patients with endocrine-resistant, ER+ MBC previously treated with endocrine therapy were assigned to one of two dose levels of alisertib (40 or 50 mg) in combination with fixed-dose fulvestrant. Ten patients enrolled, of which nine were evaluable for the primary endpoint. The median patient age was 59. All patients had secondary (acquired) endocrine resistance, and all had received prior aromatase inhibitor. Six had experienced disease progression on fulvestrant. There were no severe (grade 3+) toxicities reported during cycle 1 at either dose level. The median progression-free survival time was 12.4 months (95% CI 5.3-not met), and the 6-month clinical benefit rate was 77.8% (95% CI 40.0-8...Continue Reading

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Citations

Sep 29, 2020·Cancer Medicine·Anders BerglundJong Y Park
Sep 17, 2020·Cells·Sarah A JeffreysTherese M Becker
Jun 30, 2019·Breast Cancer Research and Treatment·Vladislav KorobeynikovElena Shagisultanova
May 18, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·S Lindsey DavisJennifer R Diamond
Feb 13, 2021·Expert Opinion on Therapeutic Patents·Xue-Li Jing, Shi-Wu Chen

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Methods Mentioned

BETA
xenograft

Clinical Trials Mentioned

NCT02860000

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