223P - Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for non-metastatic castration-resistant prostate cancer (nmCRPC)

Background

DARO is a structurally distinct androgen receptor inhibitor with a favourable safety profile, approved for treating men with nmCRPC after demonstrating significantly prolonged metastasis-free survival, compared with placebo (PBO), in the phase III ARAMIS trial: median 40.4 vs 18.4 months, respectively (HR 0.41; 95% CI 0.34–0.50; P<0.0001). We report final analyses of OS, all other secondary endpoints, and updated safety results.

Methods

1509 patients (pts) with nmCRPC were randomized 2:1 to DARO 600 mg twice daily (n=955) or PBO (n=554) while continuing ADT. Secondary endpoints included OS, times to pain progression, first cytotoxic chemotherapy, and first symptomatic skeletal event. OS analysis was planned to occur after approximately 240 deaths. Secondary endpoints were evaluated in a hierarchical order.

Results

Final analysis was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts). After unblinding at primary analysis, 170 pts crossed over from PBO to DARO. The majority of pts originally randomised to PBO (56%, including crossover pts) received a subsequent life-prolonging therapy vs 15% of pts randomised to DARO. Of pts who discontinued study treatment, the majority received subsequent docetaxel (16.8% (82/488) of DARO and 13.5% (75/554) of PBO pts).

DARO showed a statistically significant OS benefit corresponding to a 31% reduction in the risk of death vs PBO (HR 0.69; 95% CI 0.53–0.88; P=0.003), regardless of effect of crossover and subsequent therapies. All other secondary endpoints were significantly prolonged by DARO. Incidences of treatment-emergent adverse events (AEs) with ≥5% frequency were similar to those observed at primary analysis. Incidences of AEs of interest (including falls, mental impairment, and hypertension) were not increased with DARO compared with PBO when adjusted for treatment exposure.

Conclusions

DARO significantly improved OS vs PBO in men with nmCRPC. In addition, DARO delayed onset of cancer-related symptoms and subsequent chemotherapy vs PBO. With longer follow-up, safety and tolerability were favourable and consistent with the primary ARAMIS analysis.

Clinical trial identification

NCT02200614.

Editorial acknowledgement

Editorial assistance was provided by Lucy Smithers, PhD, and Annabel Ola, MSc, both 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), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Orion Pharma GmbH; Advisory/Consultancy: Curevac; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: ESSA; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: Roche. N.D. Shore: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy: Tolmar; Advisory/Consultancy: Ferring; Advisory/Consultancy: Medivation; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Myovant Sciences; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Dendreon. T.L.J. Tammela: Research grant/Funding (institution): Bayer; Advisory/Consultancy: Janssen; Research grant/Funding (institution): Lidds AB; Research grant/Funding (institution): Astellas Pharma. E. Vjaters: Advisory/Consultancy, Research grant/Funding (institution): Orion; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Ipsen. M. Jievaltas: Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Ipsen. M. Luz: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Myovant Sciences. B. Alekseev: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ferring; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): ICON Clinical Research. I. Kuss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer. M-A. Le Berre: Full/Part-time employment: Bayer. O. Petrenciuc: Full/Part-time employment: Bayer. A. Snapir: Full/Part-time employment: Orion Corporation. T. Sarapohja: Full/Part-time employment: Orion. M.R. Smith: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest.