Table 3:
Treatment-emergent adverse events
| Apalutamide + abiraterone-prednisone (n=490) |
Abiraterone-prednisone (n=489) |
|||||||
|---|---|---|---|---|---|---|---|---|
| Graded TEAEs | Grade 1-2 | Grade 3 | Grade 4 | Grade 5 | Grade 1-2 | Grade 3 | Grade 4 | Grade 5 |
| Any TEAE | 173 (35%) | 268 (55%) | 26 (5%) | 17 (3%) | 187 (38%) | 214 (44%) | 36 (7%) | 37 (8%) |
| Drug-related TEAEs | 228 (47%) | 132 (27%) | 6 (1%) | 3 (1%) | 228 (47%) | 93 (19%) | 6 (1%) | 5 (1%) |
| Serious TEAEs | 9 (2%) | 151 (31%) | 18 (4%) | 17 (3%) | 11 (2%) | 110 (22%) | 22 (4%) | 37 (8%) |
| Drug-related serious TEAEs | 1 (<1%) | 23 (5%) | 3 (1%) | 3 (1%) | 5 (1%) | 18 (4%) | 3 (1%) | 5 (1%) |
| TEAEs leading to discontinuation of the trial regimen | 28 (6%) | 38 (8%) | 8 (2%) | 9 (2%) | 7 (1%) | 22 (4%) | 9 (2%) | 23 (5%) |
| Drug-related TEAE leading to discontinuation of the trial regimen | 21 (4%) | 19 (4%) | 1 (<1%) | 2 (<1%) | 2 (<1%) | 4 (1%) | 2 (<1%) | 3 (1%) |
| TEAEs associated with death | 17 (3%) | 37 (8%) | ||||||
| Any TEAE* | ||||||||
| Fatigue | 150 (31%) | 15 (3%) | 0 | 0 | 122 (25%) | 12 (2%) | 0 | 0 |
| Back pain | 140 (29%) | 16 (3%) | 0 | 0 | 117 (24%) | 17 (3%) | 0 | 0 |
| Hypertension | 62 (13%) | 82 (17%) | 0 | 0 | 73 (15%) | 49 (10%) | 0 | 0 |
| Weight decreased | 128 (26%) | 8 (2%) | 0 | 0 | 78 (16%) | 6 (1%) | 0 | 0 |
| Arthralgia | 114 (23%) | 14 (3%) | 0 | 0 | 115 (24%) | 6 (1%) | 0 | 0 |
| Fall | 90 (18%) | 16 (3%) | 0 | 0 | 90 (18%) | 3 (1%) | 0 | 0 |
| Constipation | 96 (20%) | 0 | 0 | 0 | 94 (19%) | 2 (< 1%) | 0 | 0 |
| Diarrhoea | 85 (17%) | 7 (1%) | 0 | 0 | 71 (15%) | 3 (1%) | 0 | 0 |
| Nausea | 76 (16%) | 8 (2%) | 0 | 0 | 72 (15%) | 5 (1%) | 0 | 0 |
| Pain in extremity | 72 (15%) | 9 (2%) | 0 | 0 | 56 (11%) | 1 (< 1%) | 0 | 0 |
| Headache | 75 (15%) | 4 (1%) | 0 | 0 | 61 (12%) | 2 (< 1%) | 0 | 0 |
| Hypokalemia | 62 (13%) | 14 (3%) | 3 (1%) | 0 | 54 (11%) | 17 (3%) | 3 (1%) | 0 |
| Oedema peripheral | 76 (16%) | 0 | 0 | 0 | 70 (14%) | 3 (1%) | 0 | 0 |
| Hot flush | 74 (15%) | 0 | 0 | 0 | 56 (11%) | 0 | 0 | 0 |
| Decreased appetite | 69 (14%) | 3 (1%) | 0 | 0 | 52 (11%) | 8 (2%) | 1 (<1%) | 0 |
| Anaemia | 53 (11%) | 17 (3%) | 0 | 0 | 55 (11%) | 24 (5%) | 0 | 0 |
| Asthaenia | 57 (12%) | 9 (2%) | 0 | 0 | 58 (12%) | 7 (1%) | 0 | 0 |
| Dizziness | 58 (12%) | 3 (1%) | 0 | 0 | 46 (9%) | 0 | 0 | 0 |
| Cough | 53 (11%) | 0 | 0 | 0 | 66 (13%) | 1 (<1%) | 0 | 0 |
| Nasopharyngitis | 51 (10%) | 0 | 0 | 0 | 57 (12%) | 0 | 0 | 0 |
| Musculoskeletal pain | 49 (10%) | 1 (<1%) | 0 | 0 | 43 (9%) | 3 (1%) | 0 | 0 |
| Musculoskeletal chest pain | 47 (10%) | 1 (<1%) | 0 | 0 | 50 (10%) | 0 | 0 | 0 |
| Haematuria | 42 (9%) | 4 (1%) | 1 (<1%) | 0 | 38 (8%) | 13 (3%) | 1 (<1%) | 0 |
| Rash | 36 (7%) | 9 (2%) | 0 | 0 | 23 (5%) | 1 (<1%) | 0 | 0 |
| Urinary tract infection | 28 (6%) | 15 (3%) | 0 | 0 | 43 (9%) | 10 (2%) | 1 (<1%) | 0 |
| Bone pain | 29 (6%) | 6 (1%) | 0 | 0 | 38 (8%) | 12 (2%) | 0 | 0 |
| Contusion | 34 (7%) | 0 | 0 | 0 | 49 (10%) | 0 | 0 | 0 |
| Pneumonia | 11 (2%) | 17 (3%) | 1 (<1%) | 2 (<1%) | 13 (3%) | 9 (2%) | 0 | 1 (<1%) |
| Hyperglycaemia | 19 (4%) | 9 (2%) | 1 (<1%) | 0 | 32 (7%) | 3 (1%) | 3 (1%) | 0 |
| Blood pressure increased | 5 (1%) | 21 (4%) | 0 | 0 | 0 | 17 (3%) | 0 | 0 |
| Rash maculo-papular | 14 (3%) | 9 (2%) | 0 | 0 | 3 (1%) | 0 | 0 | 0 |
| Aspartate aminotransferase increased | 19 (4%) | 2 (<1%) | 0 | 0 | 37 (8%) | 15 (3%) | 1 (<1%) | 0 |
| Alanine aminotransferase increased | 16 (3%) | 4 (1%) | 0 | 0 | 22 (4%) | 32 (7%) | 3 (1%) | 0 |
| Blood alkaline phosphatase increased | 19 (4%) | 0 | 0 | 0 | 26 (5%) | 8 (2%) | 0 | 0 |
| Cataract | 7 (1%) | 10 (2%) | 0 | 0 | 12 (2%) | 7 (1%) | 0 | 0 |
| Syncope | 0 | 17 (3%) | 0 | 0 | 0 | 12 (2%) | 0 | 0 |
| Neutropenia | 9 (2%) | 4 (1%) | 3 (1%) | 0 | 7 (1%) | 5 (1%) | 6 (1%) | 0 |
| Acute kidney injury | 5 (1%) | 6 (1%) | 0 | 1 (<1%) | 4 (1%) | 7 (1%) | 1 (<1%) | 1 (<1%) |
| Hydronephrosis | 1 (<1%) | 10 (2%) | 1 (<1%) | 0 | 2 (<1%) | 6 (1%) | 0 | 0 |
| Sepsis | 0 | 1 (<1%) | 5 (1%) | 1 (<1%) | 1 (1<%) | 0 | 9 (2%) | 0 |
| Hyponatraemia | 4 (1%) | 2 (<1%) | 0 | 0 | 8 (2%) | 7 (1%) | 2 (<1%) | 0 |
| Pulmonary embolism | 0 | 2 (<1%) | 0 | 2 (<1%) | 1 (<1%) | 7 (1%) | 2 (<1%) | 1 (<1%) |
| TEAEs of special interest (grouped term) | ||||||||
| Hypertension | 57 (12%) | 100 (20%) | 1 (<1%) | 0 | 69 (14%) | 61 (12%) | 0 | 0 |
| Fall | 90 (18%) | 16 (3%) | 0 | 0 | 90 (18%) | 3 (1%) | 0 | 0 |
| Skin rash | 79 (16%) | 21 (4%) | 1 (<1%) | 0 | 47 (10%) | 2 (<1%) | 0 | 0 |
| Cardiac disorders† | 43 (9%) | 38 (8%) | 6 (1%) | 6 (1%) | 48 (10%) | 26 (5%) | 2 (<1%) | 18 (4%) |
| Hypokalemia‡ | 62 (13%) | 14 (3%) | 3 (1%) | 0 | 54 (11%) | 17 (3%) | 3 (1%) | 0 |
| Peripheral oedema | 90 (18%) | 1 (<1%) | 0 | 0 | 89 (18%) | 4 (1%) | 0 | 0 |
| Fracture (excluding bone metastasis–related fractures %) and osteoporosis | 54 (11%) | 20 (4%) | 0 | 0 | 52 (11%) | 7 (1%) | 0 | 0 |
| Ischaemic cerebrovascular disorders | 5 (1%) | 3 (1%) | 0 | 1 (<1%) | 7 (1%) | 2 (<1%) | 4 (1%) | 1 (<1%) |
| Seizures | 2 (<1%) | 1 (<1%) | 0 | 0 | 0 | 0 | 0 | 1 (<1%) |
Safety population. Values are n (%). All grade 3–5 events are listed in the appendix (p 6). TEAEs are those that occurred between the date of first dose of study drug and date of last dose of study drug plus 30 days. An AE is categorized as drug-related if assessed by the investigator as possibly, probably, and very likely related to study drug. Patients are counted only once for any given event, regardless of the number of times they actually experienced the event. The event experienced by the patient with the worst toxicity grade is used. If a patient had all AEs with missing toxicity grades, the patient is not counted. AEs are coded using Medical Dictionary for Regulatory Activities Version 23.0. Toxicity grade is based on National Cancer Institute common toxicity criteria, version 4.03.
AE=adverse event. TEAE=treatment-emergent adverse event.
All grade 1–2 events with an incidence of ≥10% in either treatment group and all grade 3–5 events with an incidence of ≥2% in either treatment group are shown.
See appendix p 20.
Includes only one term.