Cost-Effectiveness Analysis of Omalizumab for the Treatment of Severe Asthma in Japan and the Value of Responder Prediction Methods Based on a Multinational Trial

AbstractObjectivesOmalizumab improves health outcomes for patients with severe asthma. The purpose of this study was to conduct a cost-utility analysis of omalizumab from a societal perspective by using the results from a randomized controlled trial in Japan, and explore the efficient use of omalizumab.MethodsWe developed a Markov model to compare omalizumab add-on therapy with standard therapy. Patients transitioned between symptom-free, day-to-day, and exacerbation states. Our model had a lifetime horizon in which 5-year omalizumab add-on therapy was followed by standard therapy. Preference-based utilities were extracted from another study. We estimated the expected value of perfect information for patients' response to omalizumab.ResultsIn the base case, incremental cost-effectiveness ratio (ICER) for omalizumab add-on therapy was US $755,200 (95$614,200–$1,298,500) per quality-adjusted life-year gained, compared with standard therapy alone. One-way sensitivity analyses indicated that the results were sensitive to asthma-related mortality, exacerbation risk, and omalizumab cost. The ICER for a responder subgroup was 22$4100 (95% CI $2500–$6000) and $28 million (95$17 million–$42 million) per year, respectively.ConclusionsWith a willingness-to-pay of$45,000 per quality-adjusted life-year, omalizumab was not cost-effective in Japan. Confining omalizumab therapy to previously predicted responders, however, may be a reasonable strategy to reduce the ICER, as the cost-effectiveness was observed to improve for these patients. Further studies should be conducted to explore responder prediction methods. Decreasing the price of omalizumab would improve cost-effectiveness

Association of healthcare expenditures with aggressive versus palliative care for cancer patients at the end of life: a cross-sectional study using claims data in Japan.

[Background] End-of-life (EOL) care imposes heavy economic burdens on patients and health insurers. Little is known about the association between the types of EOL care and healthcare costs for cancer patients across various providers. [Objective] To explore the association of healthcare expenditures with benchmarking indicators of aggressive versus palliative care among terminally ill cancer patients, from the perspective of health insurers. [Design] Cross-sectional retrospective study using health insurance claims data. [Setting/participants] Cancer patients who had died in Kyoto prefecture, Japan, between April 2009 and May 2010. [Main outcome measure] Claims data were analyzed using multilevel generalized linear models to examine whether aggressive care and palliative care were associated with expenditures during the last 3 months of life, after adjusting for patient characteristics, hospital characteristics and other non-indicator procedures. [Results] We analyzed 3143 decedents from 54 hospitals. Median expenditure per patient during the last 3 months was US$13 030. Higher expenditures were associated with the aggressive care indicators of higher mortality at acute-care hospitals and use of chemotherapy in the last month of life, as well as with the palliative care indicators of increased hospice care and opioid use in the last 3 months of life. However, increased physician home care in the last 3 months was associated with lower expenditure. [Conclusions] Indicators of both aggressive and palliative EOL care were associated with higher healthcare expenditures. These results may support the coherent development of measures to optimize aggressive care and reduce the financial burdens of terminal cancer care

Survival in non-small cell lung cancer patients with versus without prior cancer

Clinical trials on cancer treatments frequently exclude patients with prior cancer, but more evidence is needed to understand their possible effects on outcomes. This study analyzed the prognostic impact of prior cancer in newly diagnosed non-small cell lung cancer (NSCLC) patients while accounting for various patient and cancer characteristics. Using population-based cancer registry data linked with administrative claims data, this retrospective cohort study examined patients aged 15–84 years diagnosed with NSCLC between 2010 and 2015 in Japan. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality in patients with versus without prior cancer. The analysis was stratified according to NSCLC stage and diagnostic time intervals between prior cancers and the index NSCLC. We analyzed 9103 patients (prior cancer: 1416 [15.6%]; no prior cancer: 7687 [84.4%]). Overall, prior cancer had a non-significant mortality HR of 1.07 (95% CI: 0.97–1.17). Furthermore, prior cancer had a significantly higher mortality hazard for diagnostic time intervals of 3 years (HR: 1.23, 95% CI: 1.06–1.43) and 5 years (1.18, 1.04–1.33), but not for longer intervals. However, prior cancer in patients with more advanced NSCLC did not show a higher mortality risk for any diagnostic time interval. Smoking-related prior cancers and prior cancers with poorer prognosis were associated with poorer survival. NSCLC patients with prior cancer do not have an invariably higher risk of mortality, and should be considered for inclusion in clinical trials depending on their cancer stage

Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: a population-based study

[Background] Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan. [Methods] Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test. [Results] Among 275, 720 newly diagnosed cancer patients, 21, 784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer. [Conclusions] The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options

Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan

BACKGROUND: Data on the risk of cardiovascular-related mortality in patients with cancer are limited. METHODS AND RESULTS: This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. CONCLUSIONS: Cancer survivors have a higher risk of fatal heart disease than the general population.Gon Y., Zha L., Sasaki T., et al. Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan. Journal of the American Heart Association 12, e029967 (2023); https://doi.org/10.1161/JAHA.123.029967

Arterial Thromboembolism in Japanese Patients With Cancer: Incidence, Predictors, and Survival Impact

Gon Y., Morishima T., Kawano T., et al. Arterial Thromboembolism in Japanese Patients With Cancer: Incidence, Predictors, and Survival Impact. JACC: CardioOncology 6, 283 (2024); https://doi.org/10.1016/j.jaccao.2024.01.006.Background: Thromboembolism is a significant complication for patients with cancer, leading to treatment interruptions and poor outcomes. Objectives: The aim of this study was to investigate the incidence of arterial thromboembolism (ATE) within cancer populations, identify the predictors of ATE, and determine its survival impact. Methods: A retrospective multicenter study was performed using data from the Osaka Cancer Registry linked with administrative data from 2010 to 2015. Patients were monitored for 5 years after cancer diagnosis, and ATE incidence was calculated with death as a competing risk. Fine and Gray competing risk regression models and Cox proportional hazards models were used to evaluate the predictors of ATE and the survival impact. Restricted mean survival time (RMST) was used to assess whether antithrombotic therapy after ATE contributed to improved survival. Results: The cohort comprised 97,448 patients with cancer (42.3% women, median age 70 years). ATE incidence displayed an annual increase, peaking 1 year after cancer diagnosis (1-, 2-, 3-, 4-, and 5-year cumulative incidences were 1.29%, 1.77%, 2.05%, 2.22%, and 2.32%, respectively). Male sex, advanced age, advanced cancer stage, and hematologic malignancies correlated with a high risk for ATE. Patients with ATE had a 2-fold increased risk for mortality compared with those without ATE. The 90-day and 1-year RMST differences for those on antithrombotic therapy were 13.3 days (95% CI: 10.4-16.2 days; P < 0.001) and 57.8 days (95% CI: 43.1-72.5 days; P < 0.001), favoring the antithrombotic therapy group. The RMST differences varied by cancer stage. Conclusions: The risk for ATE varies according to sex, age, and cancer progression and type. Antithrombotic therapy after ATE is associated with improved survival among patients with cancer

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan

Hayano E., Gon Y., Kimura Y., et al. Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan. Parkinsonism and Related Disorders 119, 105966 (2024); https://doi.org/10.1016/j.parkreldis.2023.105966.Background: The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. Methods: We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. Results: The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99–2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84–4.86), while that of those with other cancers was 1.93 (95% CI: 1.57–2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46–2.93). Conclusions: Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death

Cancer activity and bleeding events post-PCI

Purpose : Limited data exist about clinically relevant bleeding events related to antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. We investigated the risk factors for clinically relevant bleeding events in patients with cancer after PCI with stent implantation. Patients and Methods : Patients with solid cancer subjected to first PCI were divided into active (n = 45) and non-active cancer groups (n = 44). The active group included non-operable patients on treatment or with metastasis ; the non-active included those already subjected to or for whom radical surgery was planned within 3 months after the index PCI. Results : During a median follow-up of 2.2 years, 11 bleeding events occurred, with only one occurring in the non-active cancer group. Half of them occurred during the dual-antiplatelet therapy (DAPT) period, and the rest occurred during single-antiplatelet therapy (SAPT) period. Kaplan-Meier analysis showed significantly more bleeding events in the active cancer group (p = 0.010). Multivariate Cox regression hazard analysis revealed cancer activity as a significant independent risk factor for bleeding (p = 0.023) ; but not for three-point major adverse cardiovascular events. Conclusion : Clinically relevant bleeding risk after PCI was significantly lower in non-active cancer. Active cancer group had clinically relevant bleeding during both DAPT and SAPT periods

がん患者の終末期医療の質と症例数の関係

京都大学0048新制・課程博士博士(医学)甲第17418号医博第3761号新制||医||996(附属図書館)30184京都大学大学院医学研究科医学専攻(主査)教授 中山 健夫, 教授 福原 俊一, 教授 横出 正之学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Trends in clinical stage distribution and screening detection of cancer in Osaka, Japan: Stomach, colorectum, lung, breast and cervix.

We examined clinical stage distribution and proportion of screen-detected cases of stomach, colorectal, lung, female breast and cervical cancer by sex and age group using Osaka Cancer Registry data from 2000-2014. The proportion of local or in situ stage cancer had increased for all age groups in all sites, except stomach cancer in the 0-49 years group and female breast cancer in the 80 years and older group. The proportion of screen-detected cases had increased during the study period for all age groups in all cancer sites. While the proportion increased noticeably in the younger groups, there was only a slight increase in the older groups. Regarding stomach, colorectal and lung cancers, the proportion of local and in situ stage had similarly increased in the 65-79 years and 80 years and older age groups compared with younger groups, despite lower exposure to cancer screening. Regarding breast and cervical cancers, the increases in local and in situ cancer paralleled the increase in screen-detected cases. These findings suggest that the increases in early stage stomach, colorectal and lung cancers might be due not only to the expansion of screening programs but also the development of clinical diagnostic imaging or other reasons. The increases in local and in situ stage breast and cervical cancers seemed to be due to the expansion of screening. Continued monitoring of trends in cancer incidence by clinical stage may be helpful for estimating the effectiveness of screening