Adverse Events Associated with Apalutamide

Introduction to Adverse Events

Apalutamide is associated with several side effects, including skin reactions, which occur in 24% of patients compared to 5.5% with placebo, as recommended by the American College of Cardiology and other guideline societies 1
The American Urological Association and European Association of Urology report that abdominal pain, constipation, and vomiting are part of the gastrointestinal disorders associated with apalutamide 2, 3

Rash is a common side effect of apalutamide, occurring in 24% of patients compared to 5.5% with placebo, according to the National Comprehensive Cancer Network 1
Fatigue/asthenia occurs in 30.4% of patients taking apalutamide compared to 21.1% with placebo, as reported by the FDA label and clinical guidelines 1
Falls occur in 15.6% of patients taking apalutamide compared to 9.0% with placebo, highlighting the need for fall risk assessment and management 1
Fractures occur in 11.7% of patients taking apalutamide compared to 6.5% with placebo, emphasizing the importance of bone health assessment and management 1
Hypothyroidism occurs in 8.1% of patients taking apalutamide compared to 2.0% with placebo, requiring regular thyroid function monitoring and thyroid replacement therapy when indicated 1
Other common side effects include hypertension (24.8% vs 19.8%), diarrhea (20.3% vs 15.1%), nausea (18.1% vs 15.8%), weight loss (16.1% vs 6.3%), arthralgia (15.9% vs 7.5%), and dizziness (9.3% vs 6.3%) 3

Less common but clinically important side effects include mental impairment disorders (5.1% vs 3.0%) and seizures (0.2% vs 0%) 3

The National Comprehensive Cancer Network recommends regular thyroid function monitoring every 3-6 months, fall risk assessment at each visit, weight monitoring, and bone health assessment for patients taking apalutamide 1
Baseline assessments should include thyroid function tests, DEXA scan for patients with osteoporosis risk factors, blood pressure assessment, and evaluation for seizure risk and history of neurological disorders 3
Monitoring should include regular assessment for rash development, thyroid function, blood pressure, and falls risk, with regular thyroid function monitoring every 3-6 months and fall risk assessment at each visit 3, 4
The following monitoring and management strategies are recommended:

Patients with known hypothyroidism require particularly careful monitoring of thyroid function, and patients with a history of seizures should avoid apalutamide 3
Patients with cardiovascular risk factors need close monitoring for cardiovascular events, and drug interactions should be carefully evaluated before starting treatment 3

Despite the side effects, health-related quality of life was maintained in both apalutamide and placebo groups in clinical trials, suggesting that side effects can generally be managed without significant impact on overall quality of life, as reported by the Journal of the National Comprehensive Cancer Network 1, 3, 5
Overall, 10.6% of patients receiving apalutamide discontinued treatment due to adverse events compared to 7.0% of patients receiving placebo, indicating a slightly higher discontinuation rate 3