When to give denosumab (Xgeva) to patients?

When to Give Denosumab (Xgeva)

Initiate denosumab 120 mg subcutaneously every 4 weeks in all patients with bone metastases from solid tumors, regardless of symptoms, after ensuring adequate calcium/vitamin D supplementation and dental evaluation. 1

Primary Indications for Denosumab

Bone Metastases from Solid Tumors

Start immediately upon diagnosis of bone metastases in:

• Metastatic breast cancer patients - Begin denosumab or zoledronic acid in all patients with bone metastases, whether symptomatic or asymptomatic 1
• Castration-resistant prostate cancer (CRPC) - Initiate in all patients with bone metastases, regardless of symptoms 1
• Other solid tumors (lung, renal, etc.) - Use in selected patients with life expectancy >3 months who are at high risk of skeletal-related events (SREs) 1

Denosumab demonstrates superiority over zoledronic acid by delaying time to first SRE by 3.5 months in breast cancer (16.3 to 20.6 months) and 3.6 months in prostate cancer (17.1 to 20.7 months), with an 18% reduction in cumulative SREs 1, 2

Giant Cell Tumor of Bone (GCTB)

Denosumab is indicated when:

• Surgery is not possible or would be unacceptably morbid 1
• Metastatic disease is present 1
• Preoperative use is planned to solidify soft tissue components, facilitating surgical resection and reducing recurrence risk 1

Administer as monthly subcutaneous injection after three loading doses at weekly intervals 1, 2

Cancer Treatment-Induced Bone Loss

Initiate denosumab 60 mg every 6 months for:

• Postmenopausal women receiving aromatase inhibitors for breast cancer 2
• Men receiving androgen deprivation therapy for prostate cancer 2

Dosing Regimens by Indication

Bone Metastases

• 120 mg subcutaneously every 4 weeks - Do NOT extend intervals beyond 4 weeks 1, 2
• This dosing provides >90% suppression of bone turnover markers in the maximum proportion of patients 3

Giant Cell Tumor of Bone

• Three loading doses at weekly intervals, then monthly 1, 2

Cancer Treatment-Induced Bone Loss

• 60 mg subcutaneously every 6 months 2

Mandatory Pre-Treatment Requirements

Before initiating denosumab, you must:

1. Correct hypocalcemia - Treat any existing low calcium before first dose 4
2. Complete dental evaluation - Patients should finish any required dental procedures to minimize osteonecrosis of the jaw (ONJ) risk 1, 4
3. Initiate calcium and vitamin D supplementation:
   • Calcium: 1,200-1,500 mg daily 2
   • Vitamin D3: 400-800 IU daily 2
4. Ensure adequate contraception in women of childbearing potential - Continue for at least 5 months after last dose 4

Special Population: Advanced Chronic Kidney Disease

For patients with advanced CKD (including dialysis-dependent):

• Denosumab significantly increases risk of severe, potentially life-threatening hypocalcemia 4
• Measure serum calcium weekly for the first month, then monthly thereafter 4
• Provide activated vitamin D supplementation (not just standard vitamin D) 4
• Monitor closely for symptoms: muscle spasms, twitches, cramps, numbness/tingling in fingers/toes/around mouth 4

Treatment Duration

Bone Metastases

• Continue without planned interruption as long as bone disease requires treatment 2
• The pharmacokinetics of denosumab argue against intermittent treatment 2
• For stable disease after 2 years in GCTB, some centers extend intervals from 4-weekly to 8-weekly 1

Cancer Treatment-Induced Bone Loss

• Continue throughout aromatase inhibitor or androgen deprivation therapy, typically up to 2 years 2
• Extension beyond 2 years based on clinical judgment 2

Remission Consideration

• For patients in remission after 2 years, interruption of bone-modifying agent therapy is reasonable 1

Critical Safety Warnings

Do NOT Stop Abruptly

If denosumab is discontinued, you MUST initiate bisphosphonate therapy to prevent rebound bone loss and multiple vertebral fractures 2, 4

Key Adverse Events to Monitor

1. Hypocalcemia (9.6% incidence) - Most asymptomatic, grade 2, resolving by week 4 5
2. Osteonecrosis of the jaw (1.8-2.2% over 3 years) - Requires oro-maxillary surgeon involvement 1, 5
3. Atypical femoral fractures - Advise patients to report new thigh, hip, or groin pain 1, 4
4. Serious infections including cellulitis - Seek prompt medical attention 4

Contraindications

• Pregnancy 4
• Pre-existing hypocalcemia (must correct first) 4
• Prior serious hypersensitivity to denosumab 4

Common Pitfall to Avoid

Never use both Prolia and Xgeva simultaneously - they contain the same active ingredient (denosumab) at different doses for different indications 4