Superior Efficacy in Preventing Time to First SRE in Metastatic Prostate Cancer

XGEVA^®: Superior risk reduction in a head-to-head study
vs zoledronic acid^1,2

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XGEVA®: Superior risk reduction in a head-to-head study vs zoledronic acid

Data from a phase 3, randomized, double-blind, double-dummy, active-controlled study comparing XGEVA^® with zoledronic acid for the prevention of skeletal-related events (SREs) in patients with bone metastases from castration-resistant metastatic prostate cancer (N = 1,901). Zoledronic acid 4 mg was administered as an IV infusion over a minimum of 15 minutes, once every 4 weeks, in accordance with prescribing information. XGEVA^® was administered subcutaneously 120 mg, once every 4 weeks. The primary endpoint was time to first SRE (noninferiority), and the secondary endpoints were time to first SRE (superiority) and time to first and subsequent SREs (superiority). SREs are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.^1,2

*Hazard ratio (HR) is defined as the increase or decrease in likelihood of an event of interest (in this case an SRE) for one group relative to that in a comparator group.

^†P value for superiority.

XGEVA^® (denosumab) reduced the risk of first SRE by 18% vs zoledronic acid in metastatic prostate cancer
(P = 0.008, superiority)
- Pivotal phase 3 trial vs zoledronic acid (N = 1,901)

View study design details

Efficacy in other tumors¹:

XGEVA^® (denosumab) reduced the risk of first SRE by 18% vs zoledronic acid in metastatic breast cancer (P = 0.010, superiority)
- Pivotal phase 3 trial vs zoledronic acid (N = 2,046)
XGEVA^® reduced the risk of first SRE by 16% vs zoledronic acid in other metastatic solid tumors and multiple myeloma (P < 0.001, noninferiority; P = 0.060, NS for superiority)
- Pivotal phase 3 trial vs zoledronic acid (N = 1,776)

XGEVA^® is indicated for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors.

XGEVA^® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

Important Safety Information

XGEVA^® is contraindicated in patients with clinically significant hypersensitivity to any component of the product. XGEVA^® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Osteonecrosis of the jaw (ONJ) and atypical femoral fracture have been reported. XGEVA^® can cause fetal harm when administered to a pregnant woman.

Superior and Sustained Efficacy in Metastatic Prostate Cancer

XGEVA^®: Superior risk reduction in first and subsequent SREs
vs zoledronic acid^1,2

Scroll to view risk reduction for first SREs Link Arrow

XGEVA®: Superior risk reduction in first and subsequent SREs vs zoledronic acid

*Rate ratio (RR) is defined as the ratio between the incidence rates of an event across 2 groups, where each patient may have 0, 1, or any number of events. In this case, there may not be a one-to-one correspondence between the events and the patient. Each patient may have multiple events recorded.

^†P value for superiority.

^‡Cumulative mean number of SREs is the increasing average number of SREs experienced by patients over time based on multi-event analysis (1 or more SREs).

View study design details

XGEVA^® (denosumab): More time without SREs in metastatic prostate cancer

XGEVA^® extended the median time to first SRE vs zoledronic acid in a head-to-head study.¹

Median time to first SRE in patients

*Key exclusion criteria included current or prior IV bisphosphonate or oral bisphosphonate use to treat bone metastases, planned radiation therapy or surgery to bone, life expectancy < 6 months, prior or current osteonecrosis/osteomyelitis of the jaw, any planned invasive dental procedure during the study, prior malignancy within 3 years, or creatinine clearance < 30 mL/min.²

^†Data from the placebo arm (n = 208) of a randomized, controlled multicenter study (versus zoledronic acid) of 643 patients with metastatic, castration-resistant prostate cancer.³

In patients treated with XGEVA^®, the median time to first SRE was 20.7 months¹
In patients treated with zoledronic acid, the median time to first SRE was 17.1 months¹
In patients untreated for bone metastases, the median time to first SRE was 10.7 months³

Indication

XGEVA^® is indicated for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors.

XGEVA^® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

Important Safety Information

Indication

XGEVA^® (denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

XGEVA^® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

Important Safety Information

Hypersensitivity

XGEVA^® (denosumab) is contraindicated in patients with clinically significant hypersensitivity to any component of the product.

Hypocalcemia

XGEVA^® (denosumab) can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to XGEVA^® treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA^® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
Based on clinical trials using a lower dose of denosumab, patients with a creatinine clearance less than 30 mL/min or receiving dialysis are at greater risk of severe hypocalcemia compared to patients with normal renal function. The risk of hypocalcemia at the recommended dosing schedule of 120 mg every 4 weeks has not been evaluated in patients with a creatinine clearance less than 30 mL/min or receiving dialysis.

Osteonecrosis of the Jaw (ONJ)

Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA^® (denosumab), manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ.
Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA^® and periodically during XGEVA^® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA^®.
Patients who are suspected of having or who develop ONJ while on XGEVA^® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture

Atypical femoral fracture has been reported with XGEVA^® (denosumab). Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with anti-resorptive agents. A number of reports note that patients were also receiving treatment with glucocorticoids at the time of fracture. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Interruption of XGEVA^® therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Pregnancy

Women should be advised not to become pregnant when taking XGEVA^® (denosumab). If the patient is pregnant or becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Adverse Reactions

The most common adverse reactions in patients receiving XGEVA^® (denosumab) were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.

Please see Full Prescribing Information

	Xgeva^®(n = 1,026)	zoledronic acid(n = 1,020)
Median age	57 yrs	56 yrs
ECOG* status 0-1	93%	92%
Creatinine clearance ≤ 60 mL/min	12%	11%
Presence of visceral metastases	54%	51%
Prior SRE	37%	37%
> 2 bone metastases	24%	24%

	Xgeva^®(n=950)	zoledronic acid(n=951)
Median age	71 yrs	71 yrs
ECOG* status 0-1	93%	93%
Creatinine clearance ≤ 60 mL/min	24%	22%
Presence of visceral metastases	17%	19%
Prior SRE	24%	24%
> 2 bone metastases	34%	35%

BASELINE CHARACTERISTICS	Xgeva^®(n=886)	ZOLEDRONIC ACID(n=890)
Male	66%	62%
Median age	60 yrs	61 yrs
ECOG status 0-1	84%	82%
Median time from initial diagnosis of bone metastasis to randomization	2.0 mos	2.0 mos
Presence of visceral metastases	54%	50%
Prior SRE^§	50%	50%
Creatinine clearance ≤ 60 mL/min	17%	18%
Primary tumor type^\|\|
Non-small cell lung cancer	39%	40%
Multiple myeloma	10%	10%
Renal cell carcinoma	8%	10%
Small cell lung cancer	7%	5%
Other	36%	35%
Prior antineoplastic treatment	95%	96%
Systemic anticancer therapy	87%	87%
Radiotherapy	37%	40%
Surgery	46%	46%
Other	2%	2%

Baseline characteristics	XGEVA^® (denosumab) (n = 950)	zoledronic acid (n = 951)
Median age	71 yrs	71 yrs
ECOG^† status 0–1	93%	93%
Creatinine clearance ≤ 60 mL/min	24%	22%
Presence of visceral metastases	17%	19%
Prior SRE	24%	24%
> 2 bone metastases	34%	35%

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Superior Efficacy in Preventing Time to First SRE in Metastatic Prostate Cancer

XGEVA®: Superior risk reduction in a head-to-head study vs zoledronic acid1,2

Efficacy in other tumors1:

Superior and Sustained Efficacy in Metastatic Prostate Cancer

XGEVA®: Superior risk reduction in first and subsequent SREs vs zoledronic acid1,2

XGEVA® (denosumab): More time without SREs in metastatic prostate cancer

Median time to first SRE in patients

Indication

Important Safety Information

References

Contact Us

Xgeva®: Superior efficacy across multiple solid tumor types

Time to first SRE in a prespecified integrated analysis of the 3 head-to-head studies1,2

Important Safety Information

Breast cancer: 18% risk reduction in first SRE vs zoledronic acid3,6 (P = 0.010, superiority)

Breast Cancer Study: Time to First SRE

Important Safety Information

Breast Cancer Study: Baseline Characteristics

Prostate cancer: 18% risk reduction in first SRE vs zoledronic acid3,9 (P = 0.008, superiority)

Prostate Cancer Study: Time to First SRE

Important Safety Information

Prostate Cancer Study: Baseline characteristics

Other solid tumors‡/multiple myeloma: 16% risk reduction in first SRE vs zoledronic acid3,8 (P < 0.001, noninferiority; P = 0.060, NS for superiority)

Subanalysis of other solid tumors‡: 19% vs zoledronic acid1,7 (P = 0.034, superiority)

Other Solid Tumors‡/Multiple Myeloma Study: Time to First SRE

Important Safety Information

Other Solid Tumors/Multiple Myeloma Study: Baseline characteristics3,8

Xgeva®: Superior efficacy across multiple solid tumor types

Reduced the risk of first SRE in 3 individual studies including more than 50 solid tumor types

Time to first SRE across 3 individual studies

Important Safety Information

XGEVA® (denosumab): Head-to-Head Study of Patients with Prostate Cancer

Study design1

Study endpoints1

Study schema1

Important Safety Information

Baseline characteristics2-4

References

XGEVA^®: Superior risk reduction in a head-to-head study
vs zoledronic acid^1,2

Efficacy in other tumors¹:

XGEVA^®: Superior risk reduction in first and subsequent SREs
vs zoledronic acid^1,2

XGEVA^® (denosumab): More time without SREs in metastatic prostate cancer

Xgeva^®: Superior efficacy across multiple solid tumor types

Time to first SRE in a prespecified integrated analysis of the 3 head-to-head studies^1,2

Breast cancer: 18% risk reduction
in first SRE vs zoledronic acid^3,6 (P = 0.010, superiority)

Prostate cancer: 18% risk reduction
in first SRE vs zoledronic acid^3,9 (P = 0.008, superiority)

Other solid tumors^‡/multiple myeloma: 16% risk reduction in first SRE vs zoledronic acid^3,8 (P < 0.001, noninferiority; P = 0.060, NS for superiority)

Subanalysis of other solid tumors^‡: 19% vs zoledronic acid^1,7 (P = 0.034, superiority)

Other Solid Tumors^‡/Multiple Myeloma Study: Time to First SRE

Other Solid Tumors/Multiple Myeloma Study: Baseline characteristics^3,8

Xgeva^®: Superior efficacy across multiple solid tumor types

XGEVA^® (denosumab): Head-to-Head Study of Patients with Prostate Cancer

Study design¹

Study endpoints¹

Study schema¹

Baseline characteristics^2-4