7 Other Secondary and Exploratory Endpoints Once the OS results had achieved statistical signicance, the other secondary endpoints were 2 evaluated hierarchically in sequence. Time to pain progression was evaluated using data from the primary analysis as no additional data were collected for this endpoint beyond that 2,4 time. Secondary endpoints were signicantly improved by darolutamide and exploratory endpoints favored darolutamide. See Table 3 3 below. Subsequent Therapy In the placebo group, 56% of patients (309/554) received subsequent darolutamide or other life- prolonging therapy while 15% of patients (141/955) in the darolutamide group received subsequent 2 life-prolonging therapy. Subsequent life-prolonging therapy for both groups are presented in Table 4 2 below. Safety In the nal analysis (18.5 months for the doubleblind period and 25.8 months for the combined double-blind and open-label periods) of ARAMIS, the safety prole of darolutamide was consistent with the primary analysis (median exposure of 14.8 2,3 months). Overall, adverse events (AEs) were similar between the darolutamide plus ADT and placebo + ADT groups (reported in 85.7% of patients in the darolutamide plus ADT group and 79.2% of patients receiving placebo plus ADT during the double-blind period) and no new safety signals were observed in the nal analysis despite the longer treatment 2,3 exposure. Table 5 shows the Treatment Emergent Adverse Events (TEAEs) for the total safety population (N = 1508) in the primary analysis. TEAEs (all grades) occurring in ≥5% of patients reported in Table 6 below, in the darolutamide versus placebo arms, respectively, included fatigue (including asthenia) (12.1% [115/954, vs 8.7% [48/554]). Other TEAEs occurring in ≥5% in the darolutamide arm included back pain (8.8%), arthralgia (8.1%), diarrhea (6.9%), hypertension (7.3%), constipation (TEAEs occurring in 6.3%), pain in extremity (5.8%), anemia (5.6%) and hot ush (5.2%). Approximately 14% of TEAEs led to a dose modication in the darolutamide arm versus 9.4% of TEAEs in the 2 placebo arm. NE, not estimable. Endpoint, median (months) Secondary Endpoints Time to pain progression Time to initiation of cytotoxic chemotherapy Time to rst SSE Exploratory Endpoints Time to rst prostate cancer- related invasive procedure Time to initiation of subsequent antineoplastic therapy Patients who discontinued study treatment, n (%) Received life-prolonging therapy Life-prolonging therapy for CRPC received: Darolutamide Docetaxel Abiraterone, abiraterone acetate Enzalutamide Sipuleucel-T Cabazitaxel Darolutamide + ADT N=955 40.3 NE NE NE NE Placebo + ADT N=554 25.4 NE NE NE NE HR (95% CI) 0.65 (0.53-0.79) 0.58 (0.44-0.76) 0.48 (0.29-0.82) 0.42 (0.28-0.62) 0.36 (0.27-0.48) P-value <0.001 <0.001 0.005 <0.001 <0.001 3 Table 3. Outcomes of Secondary and Exploratory Endpoints Daro + ADT N=955 141 (15) – 82 (9) 29 (3) 28 (3) 1 (0.1) 1 (0.1) Daro + ADT N=955 141 (15) – 82 (9) 29 (3) 28 (3) 1 (0.1) 1 (0.1) 2 Table 4. Subsequent Life-Prolonging Therapies Daro, darolutamide. ADT, Androgen depravation therapy. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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