E. Lim (Sydney, AC, Australia)

St Vincent's Hospital and Garvan Institute of Medical Research

Author Of 2 Presentations

 On-Demand ePoster Display

48P - Abemaciclib combined with adjuvant endocrine therapy in patients from Asia with high risk early breast cancer: monarchE

Abstract

Background

monarchE demonstrated that adjuvant abemaciclib (oral CDK4 & 6 inhibitor)+endocrine therapy (ET) significantly improves invasive disease-free survival (IDFS) in HR+, HER2- high-risk early breast cancer (EBC) compared to ET alone. Here, we report the primary outcome (PO) efficacy and safety data in patients (pts) located in Asia (mainland China, Hong Kong, Japan, Korea, Singapore, and Taiwan), comprising 1,155 (20.5%) of the 5,637 pts of the intent-to-treat (ITT) population.

Methods

Pts with HR+, HER2-, high risk EBC were randomized 1:1 to abemaciclib+ET or ET alone and stratified by prior treatment (txt), menopausal status, and region (North America/Europe; Asia; Other). Exploratory analyses were conducted among pts enrolled from Asia, (median follow-up: ∼19 months in both arms).

Results

In total, 75 IDFS events were observed in pts from Asia (33 in abemaciclib+ET; 42 in ET alone). Abemaciclib+ET demonstrated numerical benefit in IDFS, reflecting a 22.3% reduction in the risk of developing invasive disease [HR (95% CI) = 0.777 (0.493, 1.227)]. Two-year IDFS rates were 93.2% in abemaciclib+ET and 90.1% in ET alone. There was also a numerical improvement in distant relapse free survival (DRFS) [HR (95% CI) = 0.758 (0.455, 1.264)], with 2-year DRFS rates of 94.4% vs 91.7%. The median txt duration of abemaciclib was 17.7 months. In the abemaciclib arm, the most frequent adverse event (AE) was diarrhea (89.5%), most were G1/2 (55.8%/28.7%). More G≥3 AEs and serious AEs were observed with abemaciclib+ET vs ET (53.5% vs 10.5% and 12.1% vs 6.3%), with neutropenia (31.5%) being the most frequent G≥3 AE. Interstitial lung disease occurred in 6.6% pts, G≥3 in 0.3% pts. G≥3 ALT and AST increases occurred in 4.2% and 3.1% pts, respectively.14.5% of abemaciclib-treated pts discontinued abemaciclib or all txt due to AEs.

Conclusions

In pts from Asia with HR+, HER2-, high-risk EBC, abemaciclib plus standard adjuvant ET led to a clinically meaningful improvement in IDFS and DRFS, consistent with benefits demonstrated in the ITT population. Safety was consistent with the known safety profile of abemaciclib. Abemaciclib is the first CDK4 & 6 inhibitor to demonstrate effective and tolerable txt in pts with high-risk EBC, including pts from Asia.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Eglantine Julle-Daniere.

Legal entity responsible for the study

Eli Lilly.

Funding

Eli Lilly.

Disclosure

Y-S. Yap: Advisory/Consultancy, Personal fees/non-financial support: Eli Lilly; Advisory/Consultancy, Personal fees/non-financial support: Novartis; Advisory/Consultancy, Personal fees/non-financial support: Pfizer; Advisory/Consultancy, Personal fees/non-financial support: AstraZeneca; Advisory/Consultancy, Personal fees/non-financial support: Eisai; Advisory/Consultancy, Personal fees/non-financial support: Roche; Advisory/Consultancy, Personal fees/non-financial support: MSD; Advisory/Consultancy, Personal fees: Inivata. S-B. Kim: Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi-Aventis; Research grant/Funding (self): DongKook Pharm Co. Y. Sagara: Honoraria (self), Personal fees: Eli Lilly; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: AstraZeneca. S. Sherwood: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. R.E. McNaughton: Full/Part-time employment: Eli Lilly. R.J. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. M. Toi: Honoraria (self), Research grant/Funding (self): Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Eli Lilly, Shimadzu, Yakult; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Kyowa-Kirin; Research grant/Funding (self): JBCRG association; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Honoraria (self): MSD; Honoraria (self): Exact Science; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: Konica Minolta; Research grant/Funding (self): Astellas; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: BMS; Honoraria (self), Research grant/Funding (self), Research Fund and Honoraria for lecture: Nippon Kayaku; Research grant/Funding (self): AFI technologies; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Advisory/Consultancy, Research grant/Funding (self): Luxonus; Research grant/Funding (self): Shionogi; Research grant/Funding (self): GL Science; Officer/Board of Directors, Board of directors: JBCRG association, Organisation for Oncology and Translational Research, Kyoto Breast Cancer Research Network. 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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