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E-Poster Display

633P - Tolerability and treatment response to darolutamide (DARO) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the phase III ARAMIS trial

Date

17 Sep 2020

Session

E-Poster Display

Presenters

Karim Fizazi

Citation

Annals of Oncology (2020) 31 (suppl_4): S507-S549. 10.1016/annonc/annonc275

Authors

N. Shore1, K. Fizazi2, M.R. Smith3, T.L. Tammela4, M. Le Berre5, O. Petrenciuc6, C. Zurth7, I. Kuss7

Author affiliations

  • 1 Carolina Urologic Research Center, Atlantic Urology Clinics, 29572 - Myrtle Beach/US
  • 2 Institut Gustave Roussy, University of Paris-Saclay, 94805 - Villejuif/FR
  • 3 Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, 02114 - Boston/US
  • 4 Tampere University Hospital, University of Tampere, Tampere/FI
  • 5 Sas, Bayer Healthcare, - - Loos/FR
  • 6 Pharmaceuticals, Bayer Healthcare, 07981 - Whippany/US
  • 7 Pharmaceuticals, Bayer AG, - - Berlin/DE
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Resources

Abstract 633P

Background

Androgen receptor inhibitors (ARIs) approved for treating nmCRPC are associated in varying degrees with certain adverse events (AEs), e.g., fatigue, risk of falls or rash. In phase III studies, dose modification and discontinuation due to AEs was higher with ARIs vs placebo. Reduced dose, compliance patterns and treatment fidelity may impact drug efficacy. Tolerability of DARO and association of prostate-specific antigen (PSA) decline in response to DARO treatment with metastasis-free survival (MFS) in the ARAMIS trial are reviewed.

Methods

1509 patients with nmCRPC and PSA doubling time (PSADT) ≤10 months were randomised 2:1 to DARO 600 mg twice daily (n=955) or placebo (PBO; n=554) while continuing androgen deprivation therapy. AEs and dose modifications were assessed every 16 weeks. The association between PSA decline from baseline in response to DARO treatment and MFS was evaluated using the Cox proportional hazards model. An association with overall survival will be investigated.

Results

DARO was well tolerated; 97.2% of patients on DARO received the full planned dose. Patients treated with DARO did not have an increase in treatment discontinuation due to AEs vs PBO (8.9% vs 8.7%). Few patients had dose modifications for any reason (15.2% vs 9.7% for DARO vs PBO). Almost all of the patients on DARO with discontinuation due to AEs or dose modifications were able to resume and re-establish the indicated dose (91.7% vs 88.9% for DARO vs PBO). In the ARAMIS trial, 50.9% of patients on DARO had a maximal PSA response (≥90% decrease from baseline) vs 1.8% of patients on PBO. Pharmacodynamic modelling showed that longer MFS was positively associated with maximum decrease in PSA from baseline.

Conclusions

Favourable tolerability of DARO at the recommended dose of 600 mg twice daily was associated with low rates of dose reduction and treatment discontinuation, which in turn may lead to extended survival with longer duration of treatment with DARO. It is important to further assess the real-world tolerance of different ARIs in men with nmCRPC.

Clinical trial identification

NCT02200614.

Editorial acknowledgement

Editorial assistance was provided by Lucy Smithers, PhD, Charlotte Simpson, PhD, and Annabel Ola, MSc, all of Scion, London, and supported by Bayer.

Legal entity responsible for the study

Bayer AG and Orion Pharma.

Funding

Bayer AG and Orion Pharma.

Disclosure

K. Fizazi: Honoraria (self), Non-remunerated activity/ies, KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche: Janssen; Honoraria (self), Non-remunerated activity/ies, KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. : Amgen; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. Bayer; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. Astellas Pharma; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. Sanofi; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. : Orion Pharma; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. Curevac; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche: AstraZeneca; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. : ESSA; Honoraria (self), KF has received personal fees and non-financial support from Janssen and Amgen, and personal fees from Bayer, Astellas Pharma, Sanofi, Orion Pharma, Curevac, AstraZeneca, ESSA, and Roche. N. Shore: Honoraria (self), Non-remunerated activity/ies, NS has received personal fees and non-financial support from Bayer and Janssen: Bayer; Honoraria (self), Non-remunerated activity/ies, NS has received personal fees and non-financial support from Bayer and Janssen: Janssen; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Tolmar; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Ferring; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Medivation; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Amgen; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Pfizer; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: AstraZeneca; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Genentech/Roche; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Myovant Sciences; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Astellas Pharma; Honoraria (self), personal fees from Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genetech/Roche, Myovant Sciences, Astellas Pharma, and Merck: Merck; Non-remunerated activity/ies, non-financial support from Dendreon: Dendreon. M.R. Smith: Honoraria (self), Research grant/Funding (self), MRS has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly: Bayer; Honoraria (self), Research grant/Funding (self), MRS has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly: Amgen; Honoraria (self), Research grant/Funding (self), MRS has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly: Janssen; Honoraria (self), Research grant/Funding (self), MRS has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly: Lilly; Honoraria (self), personal fees from Astellas Pharma, Novartis, and Pfizer: Astellas Pharma; Honoraria (self), personal fees from Astellas Pharma, Novartis, and Pfizer: Novartis; Honoraria (self), personal fees from Astellas Pharma, Novartis, and Pfizer: Pfizer. T.L. Tammela: Research grant/Funding (self): Bayer; Research grant/Funding (self): Lidds AB; Research grant/Funding (self): Astellas Pharma; Honoraria (self): Janssen. M-A. Le Berre: Full/Part-time employment: Bayer Healthcare. O. Petrenciuc: Full/Part-time employment: Bayer Healthcare. C. Zurth: Full/Part-time employment: Bayer AG. I. Kuss: Full/Part-time employment: Bayer AG.

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