A. Brufsky (Pittsburgh, PA, United States of America)

Comprehensive Breast Cancer Center, University of Pittsburgh Medical Center

Author Of 2 Presentations

 On-Demand ePoster Display

11P - A Breast Cancer Index (BCI) prognostic model for N0 HR+ breast cancer optimized for late distant recurrence

Abstract

Background

BCI is a gene expression-based assay that reports a prognostic score for risk of overall (10y) and late (≥5y) distant recurrence (DR) in HR+ early-stage breast cancer. The current study optimized the BCI prognostic model for late DR utilizing N0 patients from the translational aTTom (Trans-aTTom) study.

Methods

N0 patients in the 5y tamoxifen arm of the Trans-aTTom cohort were used to examine BCI assay cut-points based on classification of a Low-risk group with >95% 15y (10y post-randomization) late DR free survival (DRFS) as estimated by Kaplan-Meier analysis. Validation was performed in an independent multi-institutional cohort using Cox proportional hazards regression.

Results

697 N0 patients (81% ≥55y, 71% T1, 44% G2) were included. A cut-point was determined with a 15y DRFS of 95.7% and 88.7% in the BCI Low- and -High Risk groups, respectively. At 10y and 20y post-diagnosis, patients were stratified as BCI-Low Risk (45%) with a DRFS of 98.0% and 92.9%, and as BCI-High Risk (55%) with a DRFS of 94.3% and 86.4% (HR: 2.16, [1.23-3.80]; p=0.006), respectively. Independent validation in 312 patients (47% <55y, 67% T1, 62% grade 2) showed that the optimized BCI model was significantly prognostic for late DR (HR: 2.16, p=0.006), stratifying BCI Low- (45%) and High-risk (55%) patients with 96.7% and 87.9% 10-year late DRFS, respectively.

Cohorts BCI Risk Groups 10y late DRFS (95% CI) 15y late DRFS (95% CI) 20y late DRFS (95% CI)
Trans-aTTom (n=697) BCI-Low 98.0% (96.4-99.6%) 95.7% (93.3-98.1%) 92.9% (89.3-96.8%)
    BCI-High 94.3% (91.9-96.7%) 88.7% (85.3-92.2%) 86.4% (82.6-90.4%)
Multi-institutional (n=312) BCI-Low 96.7% (93.6-99.9%)
    BCI-High 87.9% (82.8-93.3%)

Conclusions

In the current study, an optimized BCI prognostic model developed in the Trans-aTTom cohort was significantly prognostic for late DR in HR+ N0 breast cancer. Additional studies in cohorts with extended follow-up are required for further validation of this BCI late DR model.

Clinical trial identification

ISRCTN17222211; NCT00003678.

Legal entity responsible for the study

Biotheranostics, Inc.

Funding

Biotheranostics, Inc.; Breast Cancer Research Foundation; Ontario Institute for Cancer Research.

Disclosure

J.M.S. Bartlett: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Biotheranostics, Inc.; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: NanoString Technologies; Honoraria (self): Oncology Education; Advisory/Consultancy: BioNTech AG; Advisory/Consultancy: Insight Genetics; Advisory/Consultancy: OncoXchange; Advisory/Consultancy: Pfizer; Advisory/Consultancy: RNA Diagnostics; Research grant/Funding (institution): Agendia; Research grant/Funding (institution): Genoptix; Research grant/Funding (institution): Stratifyer GmbH; Research grant/Funding (institution): Thermo Fisher Scientific; Licensing/Royalties, Patent - Jan 2017: Methods and Devices for Predicting Anthracycline Treatment Efficacy: Other; Licensing/Royalties, Patent - Jan 2017: Systems, Devices and Methods for Constructi (Inst): Constructi. Y. Zhang, K. Treuner: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Biotheranostics, Inc. A.M. Brufsky: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Myriad; Advisory/Consultancy: Agendia; Advisory/Consultancy: Biotheranostics, Inc. D.C. Sgroi: Advisory/Consultancy: Merrimack Pharmaceuticals; Licensing/Royalties: Biotheranostics, Inc. C.A. Schnabel: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: Biotheranostics, Inc. D.W. Rea: Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self): Eli Lilly; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Research grant/Funding (institution): Roche; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: MSD Oncology; Research grant/Funding (institution): Biotheranostics, Inc.; Research grant/Funding (institution): Celgene; Travel/Accommodation/Expenses: Eisai. All other authors have declared no conflicts of interest.

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100P - Efficacy of Enobosarm, a selective androgen receptor (AR) targeting agent, in patients with metastatic AR+/ER+ breast cancer resistant to estrogen receptor targeted agents and CDK 4/6 inhibitor in a Phase 2 clinical study

Abstract

Background

CDK 4/6 inhibitors (CDK4/6i) in combination with an ER targeted agent are the standard of care in in the treatment of metastatic ER+ breast cancer (MBC). Despite the significant increase in progression free survival seen with this combination, all patients eventually progress and therefore, there is a need for additional therapeutic options. The AR is expressed in up to 90% of ER+ breast cancer where it acts as a tumor suppressor. Enobosarm is a selective AR activating agent that does not cause virilization, and has positive clinical attributes such as promotion of bone strength and improvement of physical function. We report the clinical activity of enobosarm post CDK4/6i in women with AR+/ER MBC.

Methods

In study G200802, women with heavily pretreated AR+/ER+ MBC were randomized to receive either 9 mg (n=72) or 18 mg (n=64) of oral daily enobosarm. The safety and clear clinical activity of enobosarm in this study has previously been reported (Palmieri et al., 2020). In this analysis, the antitumor activity of targeting AR in women previously treated with and progressing on a CDK 4/6i in study G200802 was examined.

Results

There were 10 evaluable patients with measurable metastatic AR+/ER+ MBC who had progressed following treatment with a CDK 4/6i (palbociclib). Enobosarm, dosed at either 9mg or 18 mg oral daily, resulted in a clinical benefit rate of 60%, and the best objective tumor response was 33% including 2 CRs and 1 PR. The overall mean radiographic PFS in the 9 mg cohort was 10.6 months and the median was 5.2 months. Enobosarm was well tolerated.

Conclusions

We report clinical activity of enobosarm in patients with AR+/ER+ MBC with prior disease progression on ER directed therapy plus palbociclib. At the 9 mg dose, which has been selected for the phase III study, the mean rPFS was 10.6 months. These data provide support for exploring the potential clinical benefit of targeting AR with enobosarm in MBC that has progressed on a CDK4/6 inhibitor. The phase III, ARTEST trial will commence in the Q2 2021 in patients with AR+/ER+/HER2- metastatic breast cancer that has progressed on a non-steroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor.

Clinical trial identification

NCT02463032.

Legal entity responsible for the study

GTx performed the study and Veru Inc performed the data analysis.

Funding

GTx funded the clinical trial and Veru Inc supported the data analysis.

Disclosure

C. Vogel, J. O'Shaughnessy, A.M. Brufsky: Advisory/Consultancy: Veru Inc. R.H. Getzenberg: Shareholder/Stockholder/Stock options, Full/Part-time employment: Veru Inc. K.G. Barnette, M. Steiner: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Veru Inc. All other authors have declared no conflicts of interest.

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