Patterns of care and economic consequences of using bone-targeted agents for castration-sensitive prostate cancer patients with bone metastases to prevent skeletal-related events in Switzerland - the SAKK 95/16 prostate study.

BACKGROUND: International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland. METHODS: To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature. RESULTS: The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis  every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events. CONCLUSIONS: This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.

Vitamin D levels in Swiss breast cancer survivors.

BACKGROUND: Cholecalciferol (vitamin D3) is widely supplemented in breast cancer survivors because of the role of vitamin D in multiple health outcomes. METHODS: We conducted an observational study in 332 women in Eastern Switzerland with early, i.e., nonmetastatic breast cancer. Tumour-, patient-related and sociodemographic variables were recorded. Cholecalciferol intake and serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were measured at the first visit (baseline) and during a follow-up visit in a median of 210 days (range 87-857) after the first visit. Patients presenting 25(OH)D deficiency were advised to take cholecalciferol supplementation. RESULTS: At baseline, 60 (18%) patients had 25(OH)D deficiency (≤50 nmol/l, ≤20 ng/l), and 70 (21%) had insufficiency (50-74 nmol/l, 20-29 ng/l). Out of 121 patients with ongoing cholecalciferol supplementation at baseline, 25(OH)D deficiency and insufficiency was observed in 9 (7%) and 16 (13%) patients, respectively, whereas out of 52 patients with no supplementation, 15 (29%) had deficiency and 19 (37%) had insufficiency. Only 85 (26%) patients had optimal 25(OH)D levels (75-100 nmol/l, 30-40 ng/l) at baseline. Seasonal variation was significant for 25(OH)D (p = 0.042) and 1,25(OH)2D (p = 0.001) levels. Living in a rural area was associated with a higher median 25(OH)D concentration as compared with living in an urban area (87 nmol/l, range 16-216 vs 72 nmol/l, range 17-162; p = 0.001). Regular sporting activity was positively associated with 25(OH)D (p = 0.045). Body mass index was inversely related to both 25(OH)D and 1,25(OH)2D (Spearman's rho = -0.24, p <0.001; rho = -0.23, p <0.001, respectively). The levels of 25(OH)D and 1,25(OH)2D were correlated (rho = 0.21, p <0.001). Age and bone mineral density had no significant correlation with the levels of 25(OH)D. Follow-up 25(OH)D was available for 230 patients, 44 (19%) of whom had 25(OH)D deficiency and 47 (21%) had insufficiency; 25 (41.6%) initially 25(OH)D-deficient patients attained sufficient 25(OH)D levels, whereas 33 (16.5%) patients with sufficient baseline 25(OH)D levels became deficient. Only 67 (30%) patients presented optimal 25(OH)D at the follow-up. CONCLUSION: A remarkable fraction of the patients had serum 25(OH)D below (40%) or above (30%) optimal levels, and only around 30% of patients had optimal levels. Levels of 25(OH)D and 1,25(OH)2D increased on cholecalciferol supplementation, but the usual supplementation regimens were not adequate to bring 25(OH)D to the optimal range for a large proportion of patients. TRIAL REGISTRATION NUMBER: EKSG 08/082/2B.

Time trends in avoidable cancer mortality in Switzerland and neighbouring European countries 1996-2010.

QUESTION UNDER STUDY: What are the trends in avoidable cancer mortality in Switzerland and neighbouring countries? METHODS: Mortality data and population estimates 1996-2010 were obtained from the Swiss Federal Statistical Office for Switzerland and the World Health Organization Mortality Database (http://www.who.int/healthinfo/mortality_data/en/) for Austria, Germany, France and Italy. Age standardised mortality rates (ASMRs, European standard) per 100 000 person-years were calculated for the population <75 years old by sex for the following groups of cancer deaths: (1) avoidable through primary prevention; (2) avoidable through early detection and treatment; (3) avoidable through improved treatment and medical care; and (4) remaining cancer deaths. To assess time trends in ASMRs, estimated annual percentage changes (EAPCs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: In Switzerland and neighbouring countries cancer mortality in persons <75 years old continuously decreased 1996-2010. Avoidable cancer mortality decreased in all groups of avoidable cancer deaths in both sexes, with one exception. ASMRs for causes avoidable through primary prevention increased in females in all countries (in Switzerland from 16.2 to 20.3 per 100 000 person years, EAPC 2.0 [95% CI 1.4 to 2.6]). Compared with its neighbouring countries, Switzerland showed the lowest rates for all groups of avoidable cancer mortality in males 2008-2010. CONCLUSION: Overall avoidable cancer mortality decreased, indicating achievements in cancer care and related health policies. However, increasing trends in avoidable cancer mortality through primary prevention for females suggest there is a need in Switzerland and its European neighbouring countries to improve primary prevention.