XGEVA® is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy1
Meeting an unmet medical need for refractory hypercalcemia of malignancy (HCM)
HCM is a serious metabolic complication2
HCM is a serious metabolic complication in patients with advanced cancer.2
- It may be indicative of poor prognosis and may lead to renal failure, coma, and death.3,4
- Symptoms include nausea, vomiting, abdominal pain, dehydration, and confusion.5
- It can be distressing for the patient, and it must be recognized and treated aggressively.6
- The condition is caused primarily by cancer-induced bone resorption.7
- Prevalence of HCM differs by tumor type; however, rates are higher in breast, lung, and myeloma.6,8
XGEVA® is approved for HCM refractory to bisphosphonate therapy1
In an open-label, single-arm trial of patients with HCM (N=33), by day 10, approximately 64% achieved CSC* ≤ 11.5 mg/dL.1
Data from an open-label, single-arm trial that enrolled 33 patients with HCM (with or without bone metastases) refractory to treatment with intravenous bisphosphonate therapy. In this trial, refractory HCM was defined as an albumin-corrected calcium of > 12.5 mg/dL (3.1 mmol/L) despite treatment with intravenous bisphosphonate therapy in 7 to 30 days prior to initiation of XGEVA® therapy.1
*CSC=corrected serum calcium.
†Primary endpoint.
HCM may occur through one of two dominant pathways—osteolytic or humoral3
Humoral HCM:
- The second of two dominant HCM pathways. Parathyroid hormone–related protein (PTHrP) mediates this humoral arm and accounts for 80% of HCM in patients.3
- Distant primary tumors release PTHrP into the circulatory system, which drives humoral-mediated HCM. Systemic circulation transports PTHrP to bone where it increases RANK Ligand production by osteoblasts and subsequent osteoclast activation.9
- Osteoclast-driven calcium liberation from the bone matrix and inadequate renal calcium clearance due to PTHrP drive hypercalcemia.3,6
XGEVA® is the first and only RANK Ligand inhibitor in oncology1
- XGEVA® is a fully human‡ monoclonal antibody.1
- XGEVA® binds with high affinity and specificity to RANK Ligand.10
- XGEVA® decreases bone resorption and inhibits calcium release.1
‡Correlation with safety and efficacy is unknown.
XGEVA® dosing and administration1
Administer 120 mg every 4 weeks with additional 120 mg doses on days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen.1
- XGEVA® is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally.1
XGEVA® is indicated for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity1
- First and only FDA-approved treatment for giant cell tumor of bone (GCTB)11
- XGEVA® received FDA priority review status12
- FDA orphan-drug designation received for this disease12
GCTB: A rare, locally aggressive benign tumor13
GCTB is a benign tumor that is aggressive at the site and often leads to destruction of bone and extension into the surrounding soft tissues.13-15 It is estimated that there are approximately 300 to 800 new cases of GCTB annually in the United States.16 GCTB represents approximately 5% of all primary bone tumors and 20% of benign primary bone tumors in the United States.17,18
Excess RANK Ligand (RANKL) has been implicated in giant cell tumor pathogenesis impacting tumor growth and bone destruction.19 XGEVA® specifically binds to RANKL, inhibiting the formation of osteoclast-like giant cells. This MOA of XGEVA® directly impacts the bone biology of GCTB—reducing tumor growth and bone destruction.1 Administer 120 mg every 4 weeks with additional 120 mg doses on days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen.1XGEVA®: A mechanism of action (MOA) with a therapeutic effect on GCTB
XGEVA® dosing and administration1