TABLE 3.
Overall Safety Profile, AEs Occurring in ≥10% of Patients in Either Arm, Most Common Grade 3-4 AEs in ≥3 Patients, and Selected AEs
| Safety Profile | Giredestrant (n = 150) | PCET (n = 152) |
|---|---|---|
| Overall Safety Profile | ||
| All-grade AEs | 127 (84.7) | 108 (71.1) |
| Treatment-related | 70 (46.7) | 43 (28.3) |
| Grade 3-4 AEs | 26 (17.3) | 18 (11.8) |
| Treatment-related | 6 (4.0) | 4 (2.6) |
| Serious AEs | 14 (9.3) | 12 (7.9) |
| Treatment-related | 3 (2.0) | 1 (0.7) |
| Grade 5 AEs | 1 (0.7)a | 1 (0.7)b |
| AEs leading to treatment discontinuation | 2 (1.3) | 3 (2.0) |
| AEs Occurring in ≥10% of Patients in Either Arm | ||
| AST increased | 22 (14.7) | 13 (8.6) |
| Arthralgia | 18 (12.0) | 12 (7.9) |
| ALT increased | 17 (11.3) | 11 (7.2) |
| Anemia | 15 (10.0) | 9 (5.9) |
| Nausea | 15 (10.0) | 11 (7.2) |
| Most Common Grade 3-4 AEs in ≥3 Patients | ||
| Anemia | 2 (1.3) | 5 (3.3) |
| Hypertension | 3 (2.0) | 3 (2.0) |
| AST increased | 4 (2.7) | 1 (0.7) |
| Bone pain | 3 (2.0) | 1 (0.7) |
| Blood bilirubin increased | 3 (2.0) | 0 |
| Selected AEs | ||
| Hepatotoxicity | ||
| Any grade | 35 (23.3) | 21 (13.8) |
| Grade 1-2 | 30 (20.0) | 19 (12.5) |
| Grade 3-4 | 5 (3.3) | 2 (1.3) |
| Musculoskeletal pain | ||
| Any grade | 22 (14.7) | 22 (14.5) |
| Grade 1-2 | 18 (12.0) | 21 (13.8) |
| Grade 3-4 | 4 (2.7) | 1 (0.7) |
| Fatigue | ||
| Any grade | 21 (14.0) | 12 (7.9) |
| Grade 1-2 | 20 (13.3) | 12 (7.9) |
| Grade 3-4 | 1 (0.7) | 0 |
| Arthralgia | ||
| Any grade | 18 (12.0) | 12 (7.9) |
| Grade 1-2 | 18 (12.0) | 12 (7.9) |
| Nausea | ||
| Any grade | 15 (10.0) | 11 (7.2) |
| Grade 1-2 | 15 (10.0) | 10 (6.6) |
| Grade 3-4 | 0 | 1 (0.7) |
| Diarrhea | ||
| Any grade | 13 (8.7) | 6 (3.9) |
| Grade 1-2 | 12 (8.0) | 6 (3.9) |
| Grade 3-4 | 1 (0.7) | 0 |
| Dizziness | ||
| Any grade | 9 (6.0) | 7 (4.6) |
| Grade 1-2 | 9 (6.0) | 7 (4.6) |
| Vomiting | ||
| Any grade | 13 (8.7) | 2 (1.3) |
| Grade 1-2 | 11 (7.3) | 2 (1.3) |
| Grade 3-4 | 2 (1.3) | 0 |
| Hot flushes | ||
| Any grade | 6 (4.0) | 7 (4.6) |
| Grade 1-2 | 6 (4.0)c | 7 (4.6)c |
| Bradycardia | ||
| Any grade | 5 (3.3) | 2 (1.3) |
| Grade 1-2 | 5 (3.3)c | 2 (1.3)c |
| Renal toxicity | ||
| Any grade | 4 (2.7) | 1 (0.7) |
| Grade 1-2 | 4 (2.7) | 0 |
| Grade 3-4 | 0 | 1 (0.7) |
| QT prolongation (preferred term: electrocardiogram QT prolonged) | ||
| Any grade | 1 (0.7) | 2 (1.3) |
| Grade 1-2 | 1 (0.7)c | 2 (1.3)c |
| VTE (preferred term: pulmonary embolism) | ||
| Any grade | 0 | 1 (0.7) |
| Grade 5 | 0 | 1 (0.7) |
NOTE: Safety population. Data are No. of patients with ≥1 AE (%). Multiple occurrences of the same AE in one individual are counted only once. Missed doses were counted as an AE (without being graded) in the PCET arm. Preferred terms coded using MedDRA v24.1 and AE severity graded according to NCI-CTCAE v5.0. Selected AEs were defined based on the known potential and identified risks of giredestrant (fatigue, nausea, dizziness, hot flush, arthralgia, vomiting, musculoskeletal pain, bradycardia, diarrhea, hepatotoxicity, renal dysfunction, VTEs, and QT prolongation). Preferred terms (MedDRA v24.1) occurring in each category were hepatotoxicity: AST increased (14.7% v 8.6% at any grade; 2.7% v 0.7% at grade 3-4), ALT increased (11.3% v 7.2%; 1.3% v 0.7%), blood bilirubin increased (6.0% v 0.7%; 2.0% v 0), gamma-glutamyl transferase increased (2.7% v 2.0%; 0 v 1.3%), ascites (1.3% v 0.7%; 0 v 0), hyperbilirubinemia (1.3% v 0; 0 v 0), AST abnormal (0 v 0.7%; 0 v 0),c bilirubin conjugated increased (0.7% v 0; 0 v 0), hepatic failure (0 v 0.7%; 0 v 0),c hepatic pain (0.7% v 0; 0 v 0), or hepatic steatosis (0.7% v 0; 0 v 0);c musculoskeletal pain: bone pain (6.0% v 6.6%; 2.0% v 0.7%), back pain (5.3% v 2.6%; 0 v 0), pain in extremity (2.7% v 4.6%; 0 v 0.7%), myalgia (3.3% v 2.0%; 0.7% v 0), or musculoskeletal pain (0 v 2.0%; 0 v 0); fatigue: fatigue (7.3% v 3.9%; 0 v 0)c or asthenia (6.7% v 3.9%; 0.7% v 0); bradycardia: sinus bradycardia (3.3% v 0; 0 v 0)c or bradycardia (0 v 1.3%; 0 v 0);c renal toxicity: blood creatinine increased (2.7% v 0.7%; 0 v 0), azotemia (0.7% v 0; 0 v 0), blood urea increased (0.7% v 0; 0 v 0),c or renal failure (0 v 0; 0 v 0.7%).d
Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; NCI-CTCAE, National Cancer Institute's Common Terminology Criteria for Adverse Events; PCET, physician's choice of endocrine therapy; VTE, venous thromboembolism.
Ischemic stroke.
Pulmonary embolism.
Grade 1 only.
Grade 4 only.