Title :

A phase 2 study of abemaciclib in patients with brain metastases secondary to hormone receptor positive breast cancer

Author(s) :

Tolaney, Sara M. [Auteur]
Sahebjam, Solmaz [Auteur]
Le Rhun, Emilie [Auteur]
Bachelot, Thomas [Auteur]
Kabos, Peter [Auteur]
Awada, Ahmad [Auteur]
Yardley, Denise [Auteur]
Chan, Arlene [Auteur]
Conte, Pierfranco [Auteur]
Dieras, Veronique [Auteur]
Lin, Nancy U. [Auteur]
Bear, Melissa [Auteur]
Chapman, Sonya C. [Auteur]
Yang, Zhengyu [Auteur]
Chen, Yanyun [Auteur]
Anders, Carey K. [Auteur]

Journal title :

Clinical cancer research . an official journal of the American Association for Cancer Research

Abbreviated title :

Clin. Cancer Res.

Publication date :

2020-07-21

ISSN :

1078-0432

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

PURPOSE: The primary objective was to evaluate intracranial objective response rate (iORR) in patients receiving abemaciclib with brain or leptomeningeal metastases (LM) secondary to hormone receptor-positive (HR(+)) ...
Show more >PURPOSE: The primary objective was to evaluate intracranial objective response rate (iORR) in patients receiving abemaciclib with brain or leptomeningeal metastases (LM) secondary to hormone receptor-positive (HR(+)) metastatic breast cancer (MBC). Secondary objectives evaluated extracranial response, abemaciclib pharmacokinetics, brain metastases tissue exposure, and safety. PATIENTS AND METHODS: This nonrandomized, phase II study (NCT02308020) enrolled patients in tumor subtype-specific cohorts A-D: A (HR(+), HER2(-) MBC), B (HR(+), HER2(+) MBC), C (HR(+) MBC LM), and D (brain metastases surgical resection). Abemaciclib 200 mg was administered twice daily as monotherapy or with endocrine therapy, or 150 mg twice daily with trastuzumab. Cohorts A and B used a Simon two-stage design. RESULTS: In cohort A (n = 58), 3 patients were confirmed responders resulting in an iORR of 5.2% [95% confidence interval (CI), 0.0-10.9], and the intracranial clinical benefit rate (iCBR) was 24% (95% CI, 13.1-35.2). Median overall survival (OS) was 12.5 months (95% CI, 9.3-16.4). A volumetric decrease in target intracranial lesions was experienced by 38% of patients. In cohort B (n = 27), there were no confirmed intracranial responses. An iCBR of 11% (95% CI, 0.0-23.0) was observed. Median OS was 10.1 months (95% CI, 4.2-14.3). A volumetric decrease in target intracranial lesions was experienced by 22% of patients. In cohort C (n = 10), one confirmed complete parenchymal response was observed. In cohort D (n = 9), unbound brain metastases concentrations of total active abemaciclib analytes were 96- [cyclin-dependent kinase 4 (CDK4)] and 19-fold (CDK6) above in vitro IC50. Safety was consistent with prior studies. CONCLUSIONS: This study did not meet its primary endpoint. Abemaciclib was associated with an iCBR of 24% in patients with heavily pretreated HR(+), HER2(-) MBC. Abemaciclib achieved therapeutic concentrations in brain metastases tissue, far exceeding those necessary for CDK4 and CDK6 inhibition. Further studies are warranted, including assessing novel abemaciclib-based combinations.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:57:55Z