Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials

Lipton, Allan; Fizazi, Karim; Stopeck, Alison; Henry, David H.; Brown, Janet; Yardley, Denise A.; Richardson, Gary; Siena, Salvatore; Maroto, Pablo; Clemens, Michael; Bilynskyy, Boris; Charu, Veena; Beuzeboc, Philippe; Rader, Michael; Viniegra, María Eugenia Ibarrarán; Saad, Fred; Ke, Chunlei; Braun, Ada; Jun, Susie

doi:10.1016/j.ejca.2012.08.002

Cited by 502 publications

(407 citation statements)

References 30 publications

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“…The synthetic antibody denosumab specifically inhibits the maturation of osteoclasts and was shown to be superior to zoledronic acid in reducing skeletal-related events (SREs) such as surgery or radiotherapy to the bone, pathological fracture, spinal cord compression or hypercalcaemia [17]. Efficacy of these BTAs in treatment of bone metastases has been established in randomised controlled trials (RCTs) [16,18]. However, the demographic and medical characteristics of the general population often differ from patients enrolled in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

Schröder¹,

Fietz²,

Köhler

et al. 2017

European Journal of Cancer

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A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany. This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n Z 976) received BTA therapy. In 2014e2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6e70.8), 38 months (95% CI 29.4e44.2) to 28 months (95% CI 24.2 e31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.

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Section: Introductionmentioning

confidence: 99%

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

Schröder¹,

Fietz²,

Köhler

et al. 2017

European Journal of Cancer

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“…Several agents have improved overall survival (docetaxel, abiraterone acetate, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T) [1][2][3][4][5][6][7][8] or reduced morbidity (zoledronic acid and denosumab) [9][10][11] among such patients. These agents were initially investigated in men with very advanced disease whose tumors had progressed during first-line ADT, a disease state now termed castration-resistant prostate cancer.…”

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confidence: 99%

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy

et al. 2017

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BACKGROUND\ud Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design.\ud METHODS\ud We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer).\ud RESULTS\ud A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events).\ud CONCLUSIONS\ud Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476, and Current Controlled Trials number, ISRCTN78818544.

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“…In all these trials, denosumab resulted superior to zoledronic acid in preventing or delaying skeletal complications in patients with advanced malignancies and bone metastases, although no improvement in OS was observed. The most severe clinical problems linked to denosumab and highlighted by the cited studies are: hypocalcaemia and osteonecrosis of the jaw, which occurred in a higher percentage of patients treated with denosumab (3.1%) than those treated with zoledronic acid (1.3%) [111]. For these reasons, it is mandatory to perform an oral examination before starting denosumab and to administer an adequate supplement of calcium and vitamin D to all candidate patients.…”

Section: Anti-ctla-4 (Ipilimumab)mentioning

confidence: 99%

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

Bronte

Sortino

Passiglia

et al. 2014

Expert Opinion on Biological Therapy

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Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials

Cited by 502 publications

References 30 publications

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

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