What medication should be recommended for a 78-year-old man with metastatic cancer to the liver and bones, significant weight loss, and headache, currently taking Pembrolizumab (Pembro) and levetiracetam, with left tonsillar enhancement on brain MRI?

Treatment Recommendation for Brain Metastasis in a 78-Year-Old Cancer Patient

Pembrolizumab should be continued with the addition of dexamethasone for the management of brain metastasis in this 78-year-old man with metastatic cancer and left tonsillar enhancement on brain MRI. 1

Assessment of Current Clinical Situation

The patient presents with:

• 78-year-old man with metastatic cancer to liver and bones
• New symptoms: worsening weight loss and headache for past month
• Current medications: Pembrolizumab and levetiracetam
• Brain MRI showing left tonsillar enhancement, suggesting brain metastasis
• Vital signs: BP 105/60, with right lower lung findings

Treatment Algorithm for Brain Metastasis Management

First-Line Recommendation: Dexamethasone

• Start dexamethasone immediately for symptomatic brain metastasis
• Initial dosing: 16 mg/day (divided doses) 2
• Rationale: Dexamethasone is the preferred corticosteroid for brain tumor edema due to minimal mineralocorticoid activity 2
• Target: Reduce cerebral edema causing headache and neurological symptoms

Continuation of Current Therapy

• Continue pembrolizumab therapy as it has shown efficacy in brain metastases
• The American Society of Clinical Oncology (ASCO) recommends pembrolizumab for patients with asymptomatic brain metastases from various cancers 1
• Continue levetiracetam for seizure prophylaxis given the presence of brain metastasis

Radiation Consideration

• Consider stereotactic radiosurgery (SRS) or whole-brain radiation therapy (WBRT) as a next step if symptoms don't improve with corticosteroids
• WBRT has shown median survival improvement from 10 weeks to 14 weeks compared to corticosteroids alone 2

Evidence Supporting This Approach

1. Efficacy of pembrolizumab in brain metastases:

   • Pembrolizumab has demonstrated activity in melanoma brain metastases with durable responses 3
   • For patients with asymptomatic brain metastases, pembrolizumab combined with chemotherapy shows significant survival benefit (median OS 19.2 months vs 7.5 months with chemotherapy alone) 1

2. Corticosteroid management:

   • Dexamethasone is the standard treatment for symptomatic brain metastases 2
   • Systemic glucocorticoids improve neurologic function, though typically for a short time (maximum 1 month) 2

3. Safety considerations:

   • Pembrolizumab may be associated with immune-mediated side effects including colitis, hepatitis, endocrinopathies, pneumonitis, or nephritis 2
   • Regular monitoring for these adverse events is essential, especially with concurrent dexamethasone

Monitoring Plan

• Regular brain imaging to monitor response and detect progression 1
• Monitor for corticosteroid side effects (hyperglycemia, gastrointestinal bleeding, psychosis, myopathy)
• Assess for immune-related adverse events from pembrolizumab
• Evaluate neurological symptoms regularly

Important Caveats

• If the patient develops severe immune-related adverse events, pembrolizumab may need to be temporarily discontinued and higher-dose corticosteroids initiated
• Rare but serious immune-related hepatitis has been reported with pembrolizumab 4, 5
• Consider reduced frequency of pembrolizumab administration (from Q3W to Q4W) if treatment burden becomes an issue 2
• The multidisciplinary approach involving neuro-oncology, medical oncology, and radiation oncology is essential for optimal management 1

This treatment approach prioritizes symptom management while continuing effective systemic therapy that may control both intracranial and extracranial disease.