Safety of enzalutamide in patients with progressive castration-resistant prostate cancer previously treated with docetaxel-based chemotherapy: a phase II, multicenter, single-arm, open-label study

Background. Enzalutamide, an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway, is approved for patients with metastatic castration-resistant prostate cancer (CRPC). Since the phase III (AFFIRM) pivotal trial did not include Russia patients, this phase II study (NCT02124668) was performed to establish the safety of enzalutamide in patients with progressive CRPC previously treated with docetaxel-based chemotherapy in the Eastern European patients population, including the Russia. Objective: to study safety of enzalutamide in patients with progressive CRPC previously treated with docetaxel-based chemotherapy from Eastern European, including the Russia. Materials and methods . This phase II, multicenter, single-arm, open-label study was conducted at 2 sites in Russia and 2 sites in Georgia. Patients had on going androgen deprivation therapy with a gonadotropin-releasing hormone analogue (agonist or antagonist) or had a prior surgical or chiectomy. Patients completed visits on day 1, week 5, week 13 and subsequently every 12 weeks until they were discontinued from the study. The safety of enzalutamide was assessed through evaluations of adverse events (AEs), serious AEs, blood pressure, heart rate, electrocardiography and laboratory measurements. Results. Thirty patients were enrolled and received enzalutamide treatment (mean age 67.5 years (59–80 years)). Median treatment duration was 271 days (3–968 days). By the end of the study, a total of 23 (76.7 %) patients experienced 68 treatment-emergent AEs (TEAEs). The most frequently reported TEAEs (reported in ≥10 % of patients) were fatigue (n = 7 (23.3 %)), asthenia (n = 6 (20.0 %)), bone pain, metastatic pain, prostatic specific antigen increase from baseline (n = 4 (13.3 %) each) and malignant neoplasm progression (n = 3 (10.0 %)). Most TEAEs were Grade 1 or Grade 2 in severity (35 and 14 events respectively, of a total of 68 AEs). The most frequently reported Grade 3 or higher TEAEs were asthenia (n = 5 (16.7 %)) and bone pain (n = 3 (10.0 %)). Enzalutamide-related TEAEs were experienced by 7 (23.3 %) patients and consisted of the following: fatigue in 3 patients; asthenia in 2 patients; and supraventricular extrasystoles, dizziness, headache, insomnia, pollakiuria and alopecia in 1 patient, each. Six (20.0 %) patients experienced 13 serious TEAEs. The most common serious TEAE was malignant neoplasm progression (n = 3 (1 %)) due to disease progression; all others were single events. Three (10.0 %) patients had died due to serious TEAEs that occurred during the study (2 of prostate cancer progression and 1 of cardiopulmonary and liver failure). No patients experienced an enzalutamide-related Grade 3 or higher TEAEs, an enzalutamide-related serious AEs or an enzalutamide-related TEAEs leading to permanent discontinuation. No notable changes from baseline in clinical laboratory parameters or clinically meaningful abnormalities in vital signs, physical examinations, or electrocardiography were found. No cases of seizures were reported. Conclusion. In this study, enzalutamide in the Eastern European patient population, including the Russia, had a safety profile consistent with that reported in previous enzalutamide studies and no new safety signals were observed.