Side Effects of Apalutamide When Added to ADT
Apalutamide adds several significant side effects to ADT, most notably rash (23.8%), fatigue (30.4%), falls (15.6%), weight loss (16.1%), arthralgia (15.9%), fractures (11.7%), and hypothyroidism (8.1%), which should be monitored and managed proactively. 1
Common Side Effects of Apalutamide + ADT
Based on the SPARTAN trial data, the following adverse events occurred at higher rates with apalutamide compared to placebo when added to ADT:
High Frequency Side Effects (≥15%):
- Fatigue: 30.4% vs 21.1% with placebo
- Hypertension: 24.8% vs 19.8%
- Rash: 23.8% vs 5.5% (significantly higher)
- 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%
- Falls: 15.6% vs 9.0%
Other Notable Side Effects:
- Fractures: 11.7% vs 6.5%
- Dizziness: 9.3% vs 6.3%
- Hypothyroidism: 8.1% vs 2.0%
- Mental-impairment disorders: 5.1% vs 3.0%
- Seizure: 0.2% vs 0% 1
Monitoring and Management Considerations
Thyroid Function
- Hypothyroidism events were generally grade 1 or 2
- Typically identified early after starting treatment
- Baseline thyroid function tests (TSH and free T4) should be obtained before starting treatment
- Particular attention should be paid to monitoring TSH in individuals with known hypothyroidism 1, 2
- Regular monitoring during treatment is recommended
Fracture Risk
- The increased risk of fractures (11.7% vs 6.5%) requires attention
- Consider baseline DEXA scan for patients with risk factors
- Consider bone-protective agents when appropriate
Rash Management
- Rash is significantly more common with apalutamide (23.8% vs 5.5%)
- Usually appears early in treatment course
- May require topical treatments or temporary dose interruption in severe cases
Falls Prevention
- The increased risk of falls (15.6% vs 9.0%) warrants preventive measures
- Consider physical therapy referral and home safety evaluation
- Assess for contributing factors like dizziness (9.3% vs 6.3%)
Treatment Discontinuation Risk
Overall, 10.6% of patients receiving apalutamide discontinued treatment due to adverse events compared to 7.0% of patients receiving placebo 1. This indicates that while most patients tolerate the treatment, there is a slightly higher discontinuation rate that clinicians should be aware of.
Quality of Life Considerations
Despite these side effects, studies have shown that health-related quality of life was maintained in both apalutamide and placebo groups in the SPARTAN trial 1. This suggests that while side effects occur more frequently with apalutamide, they can generally be managed without significant impact on overall quality of life.
Clinical Monitoring Algorithm
Before starting treatment:
- Baseline thyroid function tests (TSH, free T4)
- Baseline DEXA scan for patients with osteoporosis risk factors
- Baseline blood pressure assessment
During first 3 months:
- Monitor for rash development (peaks early)
- Assess thyroid function at 4-6 weeks
- Monitor blood pressure
Ongoing monitoring:
- Regular thyroid function monitoring every 3-6 months
- Fall risk assessment at each visit
- Weight monitoring
- Bone health assessment
By understanding and proactively managing these side effects, clinicians can help patients maintain treatment adherence and maximize the survival benefits of apalutamide while minimizing treatment-related morbidity.