Table 3 Safety outcomes of phase 3 clinical trials evaluating NHTs (Asian sub-analyses and the landmark studies)
Agent | Disease phase | Asian study population (n) | AEs > 10% (Asian study) | AEs grade 3–5 (Asian study) | Total AEs grade 3–5 (Asian study) | Total AEs grade 3–5 (Landmark study) | Discontinuation due to AEs (Asian study) | Deaths due to AEs (Asian study) |
|---|---|---|---|---|---|---|---|---|
Abiraterone acetate | mCNPC | Hypertension (51.4%) Hypokalaemia (42.9%) Nasopharyngitis (40.0%) Weight increased (34.3%) Hot flush (31.4%) Back pain (28.6%) ALT increased, AST increased (25.7% each) Hyperglycaemia (22.9%) Rib fracture, insomnia, influenza (14.3% each) Constipation, dental caries, diarrhoea, vomiting, haematuria, hyperbilirubinaemia (11.4% each) | Hypertension (34.3%) Hypokalaemia (14.3%) Hyperglycaemia (11.4%) ALT increased, AST increased Dental caries, Diarrhoea, Bone pain (2.9% each) | 68.6% (AAP) versus 25.7% (placebo) | 68% (AAP) versus 50% (placebo) [5] | AAP group 8.6%; placebo-AAP crossover group 33.3%; placebo 11.4% | AAP 5.7%; placebo-AAP crossover none; placebo none | |
Enzalutamide | mCNPC | ARCHESb Japanese subgroup analysis (n = 92) [38] | Hot flushes (27.8%) Nasopharyngitis (25.0%) Hypertension (19.4%) Abnormal hepatic function, fractures, musculoskeletal events (13.9% each) Rash (11.1%) | Hypertension (13.9%) Abnormal hepatic function, fractures (5.6% each) Increased weight, convulsion, decreased neutrophil count, ischaemic heart disease, loss of consciousness (2.8% each) | 47% (enzalutamide) versus 25% (placebo) | Not reported | Enzalutamide 11.1%; placebo 1.8% | None |
nmCRPC | PROSPERc subgroup analysis by region (Asia vs. North America) [39] | Not reported | Not reported | Not reported | 48% (enzalutamide) versus 27% (placebo) [10] | Not reported | Not reported | |
mCRPC | PREVAILd Asian subpopulation (Japan, Korea, and Singapore) (n = 148) [40] | Fatigue, decreased appetite (20.5% each) Constipation (17.8%) URTI, falls (15.1% each) Back pain (13.7%) Pollakiuria (12.3%) Nausea (11.0%) | Back pain (2.7%) Fatigue (1.4%) | 31.5% (enzalutamide) versus 22.7% (placebo) | 53% (enzalutamide) versus 38% (placebo) [11] | Enzalutamide 4.1%; placebo 5.3% | Not reported | |
Apalutamide | mCNPC | TITANe Japanese subgroup analysis (n = 51) [42] | Skin rash (50.0%) Viral upper respiratory tract infection (39.3%) Hot flush (32.1%) Pruritus, weight increased (25.0% each) Hypertension (17.9%) Fracture, pyrexia, constipation (14.3% each) Fall, upper respiratory tract infection, fatigue, nausea, stomatitis, leukopenia, arthralgia, injection site induration (10.7% each) Hypothyroidism (7.1%) | Fracture, fall (13.0% each) Hypertension (10.7%) Skin rash (8.7%) Weight increased (3.6%) | 42.9% (apalutamide) versus 39.1% (placebo) | 7.6% (apalutamide) versus 2.7% (placebo) [12] | Apalutamide 7.1%; placebo 4.3% | Apalutamide none; placebo none |
TITANe East Asia subgroup analysis (China, Japan and Korea) (n = 62) [41] | Rash (37.3%) Hypertension (22.7%) Weight increased (21.8%) Weight decreased (18.2%) Pruritus (17.3%) Hot flush (16.4%) Upper respiratory tract infection (14.5%) Viral upper respiratory tract infection (12.7%) Arthralgia (12.7%) Constipation (11.8%) Pain in arm or leg (10.9%) Rash, generalised (10.0%) | Hypertension, rash (10.9% each) Weight increased (3.6%) Weight decreased, upper respiratory tract infection, fracture (0.9% each) | 40.9% (apalutamide) versus 38.2% (placebo) | Apalutamide 7.3%; placebo 4.5% | Apalutamide none; placebo 2.7% | |||
nmCRPC | SPARTANf Asian subpopulation (Japan, Taiwan, and South Korea) analysis (n = 126) [44] | No meaningful differences between Asian versus non-Asian patients, except for rash (38% vs. 22%) | Not reported | 39% (apalutamide) versus 46% (placebo) | 56% (apalutamide) versus 36% (placebo) [13] | Asian patients 15%; non-Asian patients 10% | Not reported | |
SPARTANf Japanese subpopulation analysis (n = 55) [45] | Skin rash (56%) | Rash maculopapular (5.9%) Hydronephrosis, rash macular, rash generalised, drug eruption, miliaria, presyncope, spinal cord compression, thrombotic cerebral infarction, decreased appetite, hyperkalaemia, lumbar spinal stenosis, lumbar vertebral fracture, hypertension, pleural effusion, pneumonia aspiration, weight decreased, amylase increased, anaemia, malignant neoplasm of renal pelvis, renal impairment, cystitis haemorrhagic, cardiac failure, cataract, prostatitis (2.9% each) | 44.1% (apalutamide) versus 23.8% (placebo) | Apalutamide 20.6%; placebo 9.5% | Apalutamide none; placebo 4.8% | |||
Darolutamide | nmCRPC | ARAMISg Japanese subpopulation analysis (n = 95) [47] | Constipation, falls (12.9% each) Fracture (11.3%) | Bladder neoplasm, hydronephrosis (3.2% each) Abscess, ALT increased, anaemia, angina pectoris, arrhythmia, AST increased, asthma, bronchitis, cataract, colon cancer, decreased appetite, fall, fracture, gingivitis, haematuria, hepatic function abnormality, influenza, iron deficiency anaemia, neutropenia, neutrophil count decreased, pancreatic carcinoma, pneumonia, postoperative ileus, pulmonary mass, rectal cancer, urinary retention (1.6% each) | 43.5% (darolutamide) versus 48.5% (placebo) | Not reported | Darolutamide 8.1%; placebo 6.1% | Not reported |