Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

Figures & data

Table 1 Combined data for adverse events from three Phase II registration trials in patients with breast cancer, prostate cancer, and other solid tumors or multiple myeloma³⁸

Adverse event	Denosumab (n = 2841)a	Zoledronic acid (n = 2836)a
Adverse events	2734 (96.2)	2745 (96.8)
Adverse events leading to study discontinuation	270 (9.5)	280 (9.9)
CTCAE Grade 3, 4, or 5 adverse events	2000 (70.4)	2009 (70.8)
Serious adverse events	1599 (56.3)	1620 (57.1)
Adverse events of interest
Acute phase reactions (first 3 days)	246 (8.7)	572 (20.2)
Hypocalcemia	273 (9.6)	141 (5.0)
Osteonecrosis of the jaw	52 (1.8)	37 (1.3)

Note:

a Patients who received at least one dose of active drug.

Abbreviation: CTCAE, Common Terminology Criteria for Adverse Events.

Table 2 Hazard ratios for development of first skeletal-related event by type

Type of SRE	Hazard ratio (95% CI)
Any SRE	0.83 (0.76–0.90), P < 0.001 in favor of denosumab
Pathological fracture	0.86 (0.76–0.96), P = 0.090 in favor of denosumab
Radiation to bone	0.77 (0.69–0.87), P ≤ 0.001 in favor of denosumab
Spinal cord compression	0.89 (0.65–1.21), P = 0.45 in favor of denosumab
Surgery to bone	0.86 (0.61–1.21), P = 0.38 in favor of denosumab
Hypercalcemia of malignancya	0.63 (0.41–0.98), P = 0.042 in favor of denosumab

Notes: Combined data from three Phase II registration trials in patients with breast cancer, prostate cancer, and other solid tumors or multiple myeloma.^38,39

a Includes data from the two Phase II registration trials in patients with breast cancer, and metastasis from solid tumors other than breast or prostate cancer and multiple myeloma. The metastatic prostate cancer trial was not included because of the low number of events.

Abbreviations: CI, confidence interval; SRE, skeletal-related events.

Table 3 Considerations for clinical decision-making

Supporting denosumab use

Supporting IV bisphosphonate use

Improved efficacy Better tolerability Longer time to development of moderate or severe bone pain (better prevention of pain) Safer in patients with progressive or baseline renal insufficiency Patients receiving nephrotoxic chemotherapy, ie, platinum chemotherapies Patients with diseases more susceptible to renal dysfunction (ie, prostate cancer) Patients with intolerance to bisphosphonates Patients currently receiving an IV bisphosphonate who experience an SRE Patients with elevated urinary NTx level despite bisphosphonate therapy Ease of subcutaneous administration Patients without port-a-cath or easy IV access Patients not receiving monthly chemotherapy infusion

Lower risk hypocalcemia Safer in patients unlikely to be compliant with oral vitamin D and calcium supplements Possibly lower risk ONJ Lower cost Greater than 10 years of experience with use in the medical community

Abbreviations: IV, intravenous; SRE, skeletal-related events; NTx, collagen type 1 crosslinked N-telopeptide; ONJ, osteonecrosis of the jaw.

LiptonAFizaziKStopeckAPrevention of skeletal-related events with denosumab or zoledronic acid: combined analysis from 3 registrational trialsAbstract number 3061, presented at the European Multidisciplinary Cancer CongressSeptember 23–27, 2011Stockholm, Sweden

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DielIJBodyJJStopeckAEffect of denosumab treatment on prevention of hypercalcemia of malignancy in cancer patients with bone metastasisAbstract number 3051, presented at the European Multidisciplinary Cancer CongressSeptember 23–27, 2011Stockholm, Sweden

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