S. Johnston (London, United Kingdom)
The Royal Marsden Hospital (Chelsea) - NHS Foundation TrustAuthor Of 1 Presentation
Adjuvant therapy for patients with HR+/HER2- EBC at high risk of recurrence (ID 338)
Presenter Of 1 Presentation
Adjuvant therapy for patients with HR+/HER2- EBC at high risk of recurrence (ID 338)
Author Of 2 Presentations
97P - Is continuing CDK4-6 inhibitor therapy safe during the COVID-19 pandemic? A UK Cancer Centre Experience
Abstract
Background
CDK4-6 inhibitors are now considered the standard of care for advanced ER-positive HER2-negative advanced breast cancer (ABC) in combination with endocrine therapy (ET). During the first wave of the COVID-19 pandemic, clinicians were uncertain what impact CDK4-6 inhibitor-induced immunosuppression may have on the risk of contracting COVID-19 or the severity of infection. Some clinicians pre-emptively reduced doses, altered schedules, or even withheld treatment, continuing ET alone. There is currently no evidence that CDK4-6 inhibitors increase the risk or severity of COVID-19 infection, although there have reports of protracted illness. We describe our experience of 203 patients receiving CDK4-6 inhibitors during the first wave and demonstrate the safety of continuing treatment during this period.
Methods
Epidemiological and clinical data were collected prospectively for patients at the Royal Marsden Hospital (RMH) and one network hospital with a ER-positive HER2-negative ABC that were receiving a CDK4-6 inhibitor between April 1st and June 30th 2020.
Results
200 patients received a CDK4-6 inhibitor in combination with ET, of which of 65/200 fulfilled local criteria to be screened with COVID-19 PCR testing and 6/65 were swab-positive. Two patients required hospital admission but there were no ICU admissions or COVID-19-associated deaths. Only 12 patients (6%) had treatment adjustments in the form of dose reduction (3/12), regime adjustment (2/12), or temporary interruption (7/12). In 9/12 cases this was a prophylactic measure due to additional risk factors; age (n=1), co-morbidities(n=3), patient choice (n=1) or overall concerns (n=4) to reduce the risk of contracting COVID-19. Results on dispensing >2 cycles at a time, telephone clinics, deferred CT scans and complications relating due to remote monitoring will also be reported.
Conclusions
Based on this snapshot during the first wave of the COVID-19 pandemic, we conclude that continuation of CDK4-6 inhibitors appears safe. This project is helping to drive a UK-wide review of CDK4-6 inhibitor treatment continuation, adjustment during the pandemic, assessing the risk of acquiring clinically severe COVID-19 infection, and subsequent cancer-related outcomes for these patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S.R.D. Johnston: Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Eisai; Research grant/Funding (institution), Clinical Trials: Roche/Genentech; Research grant/Funding (institution), Clinical Trials: Eli Lilly; Research grant/Funding (institution), Clinical Trials: Pfizer; Research grant/Funding (institution), Clinical Trials: AstraZeneca; Research grant/Funding (institution), Clinical Trials: Novartis; Research grant/Funding (institution), Laboratory studies: Pfizer; Research grant/Funding (institution), Laboratory studies: Puma Biotechnology. A. Okines: Research grant/Funding (self): Pfizer; Honoraria (self): Leo Pharma; Speaker Bureau/Expert testimony: Seagen; Advisory/Consultancy: Roche; Research grant/Funding (self): Roche; Honoraria (self): AstraZeneca; Advisory/Consultancy: Seagen. S. McGrath: Speaker Bureau/Expert testimony: Pfizer. All other authors have declared no conflicts of interest.
- C. Palmieri (Liverpool, United Kingdom)
- H. Linden (Seattle, United States of America)
- S. Birrell (Toorak Gardens, AC, Australia)
- E. Lim (Sydney, AC, Australia)
- L. Schwartzberg (Germantown, TN, United States of America)
- H. Rugo (San Francisco, CA, United States of America)
- P. Cobb (Billings, MT, United States of America)
- K. Jain (Ashland, KY, United States of America)
- C. Vogel (Miami, FL, United States of America)
- J. O'Shaughnessy (Dallas, United States of America)
- S. Johnston (London, United Kingdom)
- R. Getzenberg (Miami, United States of America)
- K. Barnette (Miami, FL, United States of America)
- M. Steiner (Miami, FL, United States of America)
- A. Brufsky (Pittsburgh, PA, United States of America)
- B. Overmoyer (Boston, United States of America)
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.