MP27-13: Long-term Safety of Darolutamide Among Patients With Metastatic Castration-resistant Prostate Cancer Who Received More Than 4 Years of Therapy

Robert Hugh Jones*, Cardiff, United Kingdom, Karim Fizazi, Villejuif, France, Nicholas D. James, Birmingham, United Kingdom, Teuvo L. Tammela, Tampere, Finland, Nobuaki Matsubara, Chiba, Japan, Frank Priou, La Roche-Sur-Yon, France, Phillipe Beuzeboc, Paris, France, Thierry Lesimple, Rennes, France, Petri Bono, Helsinki, Finland, Vesa Kataja, Kuopio, Finland, Jorge A. Garcia, Cleveland, OH, Andrew Protheroe, Oxford, United Kingdom, John Aspegren, Heikki Joensuu, Espoo, Finland, Iris Kuss, Silke Thiele, Berlin, Germany, Sabine Fiala-Buskies, Wuppertal, Germany, Eglis Vjaters, Riga, Latvia

Introduction: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor that demonstrated a consistently favorable safety and tolerability profile in previously reported phase 1/2 studies as well as in the phase 3 ARAMIS trial. In this analysis, long-term safety with extended treatment with DARO >4 years was evaluated in patients with metastatic castration-resistant prostate cancer (mCRPC) from the phase 1 ARAFOR study (NCT01784757).

Methods: This 2-part, multicenter, international study evaluated the pharmacokinetics of DARO in a 3-period crossover study that was followed by an open-label extension to assess long-term safety and tolerability. Descriptive results of patient characteristics, treatment duration, and adverse events (AEs) are summarized.

Results: Thirty patients were enrolled, 6 of whom received >4 years of DARO treatment at 600 mg twice daily. The median age was 69 years (range 58–73) and all patients were Caucasian. The median duration of treatment in ARAFOR was 63 months (range 49–90); 1 patient completed ARAFOR and entered the DARO roll-over study (NCT04464226). At baseline, normal renal function was reported for 5 patients, with 1 patient having mild renal impairment; 3 patients had normal hepatic function and 3 had mild hepatic impairment. Eastern Cooperative Oncology Group performance status was 0 for 5 patients and 1 for 1 patient, and Gleason score was 7 for 4 patients at baseline. No patient received prior chemotherapy. All 6 patients reported AEs; 3 patients reported diarrhea, and 2 patients each reported abdominal pain, nausea, arthralgia, hematuria, influenza, anemia, dysuria, fall/accident, rib fracture, solar dermatitis, and decreased weight. Grade 3 AEs occurred in 5 patients and serious AEs in 4 patients; no individual grade 3 or serious AE occurred in more than 1 patient and none were judged to be related to darolutamide. Treatment-related AEs (tinnitus, fatigue, solar dermatitis) were reported in 2 patients and were grade 1 in worst severity. No patients discontinued DARO due to AEs.

Conclusions: In this small group of mCRPC patients from the phase 1 ARAFOR study, long-term treatment with DARO beyond 4 years was generally well tolerated and no new safety signals were observed.

Source of Funding: Bayer AG and Orion Pharma