Abstract 201P
Background
Asymptomatic nmCRPC patients (pts) would benefit from treatments (Tx) that delay disease progression and maintain quality of life (QoL), with minimal Tx-related adverse events (AEs). In ARAMIS, darolutamide (DARO) prolonged metastasis-free survival vs placebo (PBO) (40 vs 18 months; HR 0.41; 95% CI 0.34–0.50; P < 0.001); impact on prostate-specific antigen (PSA), disease progression, safety, and QoL in ARAMIS is reported here.
Methods
Pts were randomized to DARO 600 mg twice daily (n = 955) or PBO (n = 554), while androgen deprivation therapy continued in both arms. Secondary/exploratory endpoints included safety, time to cytotoxic chemotherapy, time to antineoplastic therapy, time to PSA progression, and QoL.
Results
DARO substantially delayed times to PSA progression (33 vs 7 months; HR 0.13; 95% CI 0.11–0.16; P < 0.001), cytotoxic chemotherapy (not reached [NR] vs 38 months; HR 0.43; 95% CI 0.31–0.60; P < 0.001), and antineoplastic therapy (NR vs NR; HR 0.33; 95% CI 0.23–0.47; P < 0.001) vs PBO. The distribution of sites of distant metastases was similar between groups: 60/130 (46%) and 62/158 (39%) had bone-only metastases, 41/130 (32%) and 63/158 (40%) had lymph node-only metastases, while 17/130 (13%) and 22/158 (14%) had both lymph node and bone metastases, in the DARO and PBO groups, respectively. Distant metastases at other sites were also similar, occurring in 12/130 (9%) and 11/158 (7%) of pts in the DARO and PBO groups, respectively. Incidences of Tx-emergent AEs with ≥5% frequency or of grade 3–5 were comparable between DARO and PBO; none except fatigue occurred in > 10% of pts. Discontinuation rates due to AEs were 8.9% with DARO and 8.7% with PBO. AEs noted with other androgen receptor inhibitors (including fracture, falls, seizures, hypertension and cognitive disorder) showed minimal or no difference in incidence between groups. DARO maintained QoL, and delayed the onset of pain and disease-related urinary symptoms compared with PBO.
Conclusions
DARO delays disease progression and subsequent Tx for metastatic castration-resistant prostate cancer vs PBO, maintaining QoL without increasing incidence of key AEs.
Clinical trial identification
NCT02200614.
Editorial acknowledgement
Medical writing support for the development of this abstract was provided by Lucy Smithers, PhD, and editorial support, including formatting, proofreading, and submission was provided by Beth King, both of Scion Medica, London, supported by Bayer according to Good Publication Practice guidelines.
Legal entity responsible for the study
Orion Corporation, Orion Pharma and Bayer AG.
Funding
Orion Corporation and Bayer AG.
Disclosure
J.S-T. Pang: Non-remunerated activity/ies, Writing support: Bayer. N. Shore: Advisory / Consultancy, Research grant / Funding (self): Ferring; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Dendreon; Advisory / Consultancy, Research grant / Funding (self): Tolmar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self): Myovant Sciences; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy, Research grant / Funding (self): Nymox. M.R. Smith: Honoraria (self): Amgen; Honoraria (self): Astellas; Honoraria (self): Bayer; Honoraria (self): Clovis; Honoraria (self): Gilead; Honoraria (self): Janssen; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer. T.L. Tammela: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): Lidds AB; Advisory / Consultancy, Research grant / Funding (self): Astellas. E. Vjaters: Research grant / Funding (self): Ipsen; Research grant / Funding (self): Bayer; Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Orion. M. Jievaltas: Honoraria (self): Bayer; Honoraria (self): Ipsen; Honoraria (self): Janssen. M. Luz: Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Research grant / Funding (self): Janssen; Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (self): Ferring; Speaker Bureau / Expert testimony: Sanofi. B. Alekseev: Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Astellas; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Ferring; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Janssen; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: MSD; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), Non-remunerated activity/ies: Sanofi. I. Kuss: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bayer. M-A. Le Berre: Full / Part-time employment: Bayer Healthcare. A. Snapir: Full / Part-time employment: Orion Pharma. T. Sarapohja: Full / Part-time employment: Orion Corporation. K. Fizazi: Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self): Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Curevac; Advisory / Consultancy: ESSA; Advisory / Consultancy: Orion Pharma; Advisory / Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.
Resources from the same session
51P - Enhancing the anti-breast tumour activity of STING through a novel sting transcriptional regulator
Presenter: Hanchu Xiong
Session: Poster display session
Resources:
Abstract
52P - Reverse Warburg effect-related mitochondrial activity and 18F-FDG uptake in invasive ductal carcinoma
Presenter: Byung Wook Choi
Session: Poster display session
Resources:
Abstract
53P - Phase II study of atorvastatin in combination with radiotherapy and temozolomide in patients with glioblastoma (ART): Final analysis report
Presenter: Abdullah Altwairgi
Session: Poster display session
Resources:
Abstract
54P - Association between Parkinson’s disease and brain tumours: A nationwide population-based cohort study
Presenter: Joo-hyun Park
Session: Poster display session
Resources:
Abstract
55P - Toxicity profiles of treatment with modern fractionated radiotherapy, contemporary stereotactic radiosurgery, or transsphenoidal surgery in non-functioning pituitary macroadenoma
Presenter: Kevin Sheng-Po Yuan
Session: Poster display session
Resources:
Abstract
56P - Hippocampal avoidance in WBRT for metastases: Comparative neurocognitive and dosimetric assessment
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
57P - Multidisciplinary brain metastasis clinic: Is it effective and worthwhile?
Presenter: Annu Rajpurohit
Session: Poster display session
Resources:
Abstract
58P - Functional status as a determinant prognostic factor for overall survival in adult patients with medulloblastoma treated with chemotherapy and radiotherapy
Presenter: Juan Ayala Alvarez
Session: Poster display session
Resources:
Abstract
59P - Pattern of care in high-grade gliomas after recurrence
Presenter: Nandini Menon
Session: Poster display session
Resources:
Abstract
60P - Five fractions plus “SRS” boost combined with temozolamide for newly diagnosed and recurrent glioblastoma multiforme (GBM)
Presenter: Azhar Rashid
Session: Poster display session
Resources:
Abstract