Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: Neal D Shore*, Myrtle Beach, SC, Matthew R Smith, Boston, MA, Tuevo LJ Tammela, Tampere, Finland, Albertas Ulys, Vilnius , Lithuania, Eglis Vjaters, Riga, Latvia, Sergey Polyakov, Minsk, Belarus, Mindaugas Jievaltas, Kaunas, Lithuania, Murilo Luz, Curitiba, Brazil, Boris Alekseev, Moscow, Russian Federation, Iris Kuss, Berlin, Germany, Marie A Le Berre, Loos, France, Amir Snapir, Toni Sarapohja, Espoo, Finland, Karim Fizazi, Villejuif, France
Introduction: Asymptomatic nonmetastatic castrate-resistant prostate cancer (nmCRPC) patients (pts) would benefit from treatments (Tx) that delay disease progression with minimal Tx-related adverse events (AEs). Darolutamide (DARO) is a structurally unique androgen receptor (AR) antagonist for which in vitro and phase I/II studies suggest low risk of AEs and drug-drug interaction. DARO prolonged metastasis-free survival (MFS) compared with placebo (PBO) (40 vs 18 mo; HR 0.41; 95% CI 0.34-0.50; P<0.001) in ARAMIS. Interim overall survival (OS) favored DARO (HR 0.71; 95% CI 0.50-0.99; P=0.045). DARO's impact on prostate-specific antigen (PSA), disease progression, safety, and quality of life (QoL) in ARAMIS is reported here.
Methods: 1509 pts were randomized 2:1 to DARO 600 mg (two 300 mg tablets) twice daily (n=955) or PBO (n=554) while continuing androgen deprivation therapy. The primary end point was MFS. Secondary and exploratory endpoints included OS, time to cytotoxic chemotherapy, time to antineoplastic therapy, and safety. Exploratory endpoints included time to PSA progression and QoL, assessed by the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and the European Organisation for Research and Treatment of Cancer QoL Prostate Cancer module (EORTC-QLQ-PR25).
Results:DARO elicited an overall PSA response of ≥50% in 84% of pts vs 8% with PBO; 51% of pts had ≥90% PSA decline with DARO. DARO substantially delayed time to PSA progression (33 vs 7 mo; HR 0.13; 95% CI 0.11-0.16; P<0.001), time to cytotoxic chemotherapy (not reached [NR] vs 38 mo; HR 0.43; 95% CI 0.31-0.60; P<0.001), and time to antineoplastic therapy (NR vs NR; HR 0.33; 95% CI 0.23-0.47; P<0.001) compared with PBO. Incidences of Tx-emergent AEs with ≥5% frequency or grade 3-5 were comparable between study arms; only fatigue had an incidence of >10%. AE-related discontinuation rates were similar between study arms. AEs of interest (including fracture, falls, seizures, weight decrease, hypertension, and cognitive disorder) showed minimal or no difference in incidence between study arms. QoL was similar for DARO and PBO; differences in least-squares mean time-adjusted area under curve scores for BPI-SF, FACT-P, and EORTC-QLQ-PR25 subscales consistently favored DARO.
Conclusions: DARO delays disease progression and subsequent Tx for metastatic CRPC compared with PBO, preserving QoL without increasing the prevalence of key AEs.
Source of Funding: Bayer AG and Orion Pharma