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ABSTRACT: INTRODUCTION: Patients with bone metastases often experience skeletal-related events (SREs). Although cost-utility models are used to examine treatments for metastatic cancer, limited information is available on utilities of SREs. The purpose of this study was to estimate the disutility of four SREs: spinal cord compression, pathological fracture, radiation to bone, and surgery performed to stabilize a bone. METHODS: General population participants from the UK and Canada completed time trade-off (TTO) interviews to assess the utility of health states drafted based on literature review, clinician interviews, and patient interviews. Respondents first rated a health state describing cancer with bone metastases. Then, the SREs were added to this health state. RESULTS: Interviews were completed with 187 participants (50.8 % male, 80.2 % white). Cancer with bone metastases without an SRE had a mean utility of 0.47 (SD = 0.43) on a standard utility scale (1 = full health, 0 = death). Of the SREs, spinal cord compression was associated with the greatest disutility (i.e., the utility decrease): -0.32 with paralysis and -0.22 without paralysis. Surgery had a disutility of -0.07. Leg, arm, and rib fractures had disutilities of -0.06, -0.04, and -0.03. Two weeks of daily radiation treatment had a disutility of -0.06, while two radiation appointments had the smallest impact on utility (-0.02). CONCLUSION: All SREs were associated with statistically significant utility decreases, suggesting a perceived impact on quality of life beyond the impact of cancer with bone metastases. The resulting disutilities may be used in cost-utility models examining treatments to prevent SREs secondary to bone metastases.
The European Journal of Health Economics 01/2013; · 1.50 Impact Factor
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Allan Lipton,
Karim Fizazi,
Alison T Stopeck,
David H Henry,
Janet E Brown,
Denise A Yardley,
Gary E Richardson,
Salvatore Siena,
Pablo Maroto,
Michael Clemens,
Boris Bilynskyy,
Veena Charu,
Philippe Beuzeboc,
Michael Rader,
Maria Viniegra,
Fred Saad,
Chunlei Ke, Ada Braun,
Susie Jun
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ABSTRACT: Patients with bone metastases from advanced cancer often experience skeletal-related events (SRE), which cause substantial pain and morbidity. Denosumab, a fully human monoclonal antibody that inhibits RANK Ligand (RANKL), is a novel bone-targeted agent with a distinct mechanism of action relative to the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned analysis evaluates the efficacy and safety of denosumab versus zoledronic acid across three pivotal studies.
Patient-level data from three identically designed, randomised, double-blind, active-controlled, phase 3 trials of patients with breast cancer, prostate cancer, other solid tumours or multiple myeloma were combined. End-points included time to first SRE, time to first and subsequent (multiple) SRE, adverse events, time to disease progression and overall survival.
Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21months, reducing the risk of a first SRE by 17% (hazard ratio, 0.83 [95% confidence interval (CI): 0.76-0.90]; P<0.001). Efficacy was demonstrated for first and multiple events and across patient subgroups (prior SRE status; age). Disease progression and overall survival were similar between the treatments. In contrast to zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status, and was not associated with acute-phase reactions. Hypocalcaemia was more common for denosumab. Osteonecrosis of the jaw occurred at a similar rate (P=0.13).
Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer.
European journal of cancer (Oxford, England: 1990) 09/2012; 48(16):3082-92. · 4.12 Impact Factor
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Charles S Cleeland,
Jean-Jacques Body,
Alison Stopeck,
Roger von Moos,
Lesley Fallowfield,
Susan D Mathias,
Donald L Patrick,
Mark Clemons,
Katia Tonkin,
Norikazu Masuda,
Allan Lipton,
Richard de Boer,
Stefania Salvagni,
Celia Tosello Oliveira,
Yi Qian,
Qi Jiang,
Roger Dansey, Ada Braun,
Karen Chung
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ABSTRACT: BACKGROUND: In this study, the authors evaluated the effect of denosumab versus zoledronic acid (ZA) on pain in patients with advanced breast cancer and bone metastases. METHODS: The prevention of pain, reduction in pain interference with daily life activities, and the proportion of patients requiring strong opioid analgesics were assessed in a randomized, double-blind, double-dummy phase 3 study comparing denosumab with ZA for preventing skeletal-related events in 2046 patients who had breast cancer and bone metastases. Patients completed the Brief Pain Inventory-Short Form at baseline and monthly thereafter. RESULTS: Fewer patients who received denosumab reported a clinically meaningful worsening of pain severity (≥2-point increase) from baseline compared with patients who received ZA, and a trend was observed toward delayed time to pain worsening with denosumab versus ZA (denosumab, 8.5 months; ZA, 7.4 months; P = .08). In patients who had no/mild pain at baseline, a 4-month delay in progression to moderate/severe pain was observed with denosumab compared with ZA (9.7 months vs 5.8 months; P = .002). Denosumab delayed the time to increased pain interference by approximately 1 month compared with ZA (denosumab, 16.0 months; ZA, 14.9 months; P = .09). The time to pain improvement (P = .72) and the time to decreased pain interference (P = .92) were similar between the groups. Fewer denosumab-treated patients reported increased analgesic use from no/low use at baseline to strong opioid use. CONCLUSIONS: Denosumab demonstrated improved pain prevention and comparable pain palliation compared with ZA. In addition, fewer denosumab-treated patients shifted to strong opioid analgesic use. Cancer 2012. © 2012 American Cancer Society.
Cancer 09/2012; · 4.77 Impact Factor
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Miguel Martin,
Richard Bell,
Hugues Bourgeois,
Adam Brufsky,
Ingo Diel,
Alexandru Eniu,
Lesley Fallowfield,
Yasuhiro Fujiwara,
Jacek Jassem,
Alexander H G Paterson,
Diana Ritchie,
Günther G Steger,
Alison Stopeck,
Charles Vogel,
Michelle Fan,
Qi Jiang,
Karen Chung,
Roger Dansey, Ada Braun
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ABSTRACT: Denosumab was shown to be superior to zoledronic acid in preventing skeletal related events (SRE) in patients with breast cancer and bone metastases in a randomized, double-blind phase III study. We evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL).
Patients were randomized 1:1 to receive subcutaneous denosumab 120 mg (n = 1,026) and intravenous placebo, or intravenous zoledronic acid 4 mg (n = 1,020) and subcutaneous placebo every 4 weeks. Analyses reported here include the proportion of patients with one or multiple on-study SREs, time to first radiation to bone, time to first SRE or hypercalcemia of malignancy, and change in HRQoL (functional assessment of cancer therapy-general).
Fewer patients receiving denosumab than zoledronic acid had an on-study SRE (31% vs. 36%, P = 0.006). The incidence of first radiation to bone was 12% (n = 123) with denosumab versus 16% (n = 162) with zoledronic acid. Denosumab prolonged the time to first radiation to bone by 26% versus zoledronic acid (HR, 0.74; 95% confidence interval [CI], 0.59-0.94, P = 0.012) and prolonged the time to first SRE or hypercalcemia of malignancy by 18% (HR, 0.82; 95% CI, 0.70-0.95; P = 0.007). Ten percent more patients had a clinically meaningful improvement in HRQoL with denosumab relative to zoledronic acid, regardless of baseline pain levels.
Denosumab was superior to zoledronic acid in reducing bone-related complications of metastatic breast cancer and maintained HRQoL, providing an efficacious, well-tolerated treatment option for patients with bone metastases from breast cancer.
Clinical Cancer Research 08/2012; 18(17):4841-9. · 7.74 Impact Factor
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ABSTRACT: Background: Although cost utility models are often used to estimate the value of treatments for metastatic cancer, limited information is available on the utility of common treatment modalities. Bisphosphonate treatment for bone metastases (BM) is frequently administered via intravenous (IV) infusion, while a recently approved treatment to prevent skeletal-related events (SREs) of BM is administered as a subcutaneous (SC) injection. This study estimated the impact of these treatment modalities on health state (HS) preference. Methods: Participants from the UK general population completed time trade-off interviews to assess the utility of HS vignettes. Respondents first rated a HS representing cancer with BM. Subsequent HSs added descriptions of treatment modalities (ie, injection or infusion) to this basic HS. To represent a range of possible treatment experiences, the two treatment modalities were presented with and without chemotherapy (chemotx), and infusion characteristics were varied by duration (30 minutes or 2 hours) and renal monitoring. Results: A total of 121 participants completed the interviews (47.9% male, 76.9% white). Cancer with BM had a mean utility of 0.40 on a standard utility scale (1 = full health; 0 = death). Adding an injection resulted in a mean utility decrease (ie, disutility) of -0.004. The 30 minute and 2 hour infusions had mean disutilities of -0.02 and -0.04, respectively. Mean disutility of the 30 minute infusion was greater with renal monitoring (-0.05 with same-day blood draw; -0.07 with blood draw 2 days prior). Chemotx was associated with substantial disutility (-0.17). For the HS of BM with chemotx, the mean disutilities of injection, 30 minute infusion, and 2 hour infusion, were -0.02, -0.03, and -0.04, respectively. Disutility associated with injection was significantly smaller than the disutility of both the 30 minute and 2 hour infusions (p < 0.05), regardless of chemotx status. Conclusions: Respondents perceived an inconvenience with each type of BM treatment, but injections were preferred over infusions. The resulting utilities may be used in cost utility models examining the value of treatments for the prevention of SREs in patients with BM.
ASCO; 01/2012
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Alison T Stopeck,
Allan Lipton,
Jean-Jacques Body,
Guenther G Steger,
Katia Tonkin,
Richard H de Boer,
Mikhail Lichinitser,
Yasuhiro Fujiwara,
Denise A Yardley,
María Viniegra,
Michelle Fan,
Qi Jiang,
Roger Dansey,
Susie Jun, Ada Braun
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ABSTRACT: This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases.
Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression).
Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39).
Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.
Journal of Clinical Oncology 11/2010; 28(35):5132-9. · 18.37 Impact Factor
