Accelerating glioblastoma therapeutics via venture philanthropy.

Development of curative treatments for glioblastoma (GBM) has been stagnant in recent decades largely because of significant financial risks. A portfolio-based strategy for the parallel discovery of breakthrough therapies can effectively reduce the financial risks of potentially transformative clinical trials for GBM. Using estimates from domain experts at the National Brain Tumor Society (NBTS), we analyze the performance of a portfolio of 20 assets being developed for GBM, diversified across different development phases and therapeutic mechanisms. We find that the portfolio generates a 14.9% expected annualized rate of return. By incorporating the adaptive trial platform GBM AGILE in our simulations, we show that at least one drug candidate in the portfolio will receive US Food and Drug Administration (FDA) approval with a probability of 79.0% in the next decade.

Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: an updated evaluation using a partitioned survival model.

PURPOSE: A first cost-effectiveness analysis has raised a strong concern regarding the cost of tumor treatment fields (TTF) added to maintenance temozolomide for patients with glioblastoma. This evaluation was based on effectiveness outcomes from an interim analysis of the pivotal trial, moreover it used a "standard" Markov model. Our objective was to update the cost-effectiveness evaluation using the more flexible potential of the "partitioned survival" model design and using the latest effectiveness data. METHODS: We developed the model with three mutually exclusive health states: stable disease, progressive disease, and dead. Good fit parametric models were developed for overall survival and progression free survival and these generated clinically plausible extrapolations beyond the observed data. We adopted the perspective of the French national health insurance and used a 20-year time horizon. Results were expressed as cost/life-years (LY) gained (LYG). RESULTS: The base case model generated incremental benefit of 0.604 LY at a cost of €453,848 which, after 4% annual discounting of benefits and costs, yielded an incremental cost effectiveness ratio (ICER) of €510,273/LYG. Using sensitivity analyses and bootstrapping methods results were found to be relatively robust and were only sensitive to TTF device costs and the modelling of overall survival. To achieve an ICER below €100,000/LYG would require a reduction in TTF device cost of approximately 85%. CONCLUSIONS: Using a different type of model and updated survival outcomes, our results show TTF remains an intervention that is not cost-effective, which greatly restrains its diffusion to potentially eligible patients.

Effect of patient age on glioblastoma perioperative treatment costs: a value driven outcome database analysis.

INTRODUCTION: Identification of groups of patients or interventions with higher associated treatment costs may be beneficial in efforts to decrease the overall financial burden of glioblastoma (GBM) treatment. The authors' objective was to evaluate perioperative surgical treatment cost differences between elderly and nonelderly patients with GBM using the Value Driven Outcome (VDO) database. METHODS: The authors obtained data from a retrospective cohort of GBM patients treated surgically (resection or biopsy) at their institution from August 2011 to February 2018. Data were compiled using medical records and the VDO database. RESULTS: A total of 181 patients with GBM were included. Patients were grouped into age < 70 years at time of surgery (nonelderly; n = 121) and ≥ 70 years (elderly; n = 60). Costs were approximately 38% higher in the elderly group on average (each patient was mean 0.68% of total cohort cost vs. 0.49%, p = 0.044). Higher age significantly, but weakly, correlated with higher treatment cost on linear regression analysis (p = 0.007; R2 = 0.04). Length of stay was significantly associated with increased cost on linear regression (p < 0.001, R2 = 0.84) and was significantly longer in the elderly group (8.7 ± 11.3 vs. 5.2 ± 4.3 days, p = 0.025). The cost breakdown by facility, pharmacy, supply/implants, imaging, and laboratory costs was not significantly different between age groups. Elderly patients with any postoperative complication had 2.1 times greater total costs than those without complication (p = 0.094), 2.9 times greater total costs than nonelderly patients with complication (p = 0.013), and 2.3 times greater total costs than nonelderly patients without complication (p = 0.022). CONCLUSIONS: GBM surgical treatment costs are higher in older patients, particularly those who experience postoperative complications.

A Real-World Claims Analysis of Costs and Patterns of Care in Treated Patients with Glioblastoma Multiforme in the United States.

BACKGROUND: Patients with glioblastoma multiforme (GBM) have a poor prognosis and high likelihood of recurrence. Routine care for incident cases in the United States involves surgical resection, followed by radiation therapy (RT) with concurrent and adjuvant temozolomide. Real-world data reporting the treatments and health care burden associated with GBM are limited. OBJECTIVE: To assess patterns of care, health care resource utilization (HCRU), and costs associated with treatment of GBM in the United States. METHODS: This study is a retrospective claims database analysis. Adult patients with a GBM diagnosis (index date) between January 1, 2010, and June 30, 2016, who had undergone brain surgery within 90 days of the index date, had received temozolomide and/or RT up to 90 days after index date, and had at least 6 months of continuous enrollment before the index date, were identified. Patients were excluded if they had (a) another primary cancer within 6 months pre-index, (b) secondary brain metastases, or (c) received temozolomide and/or RT pre-index. Baseline characteristics, treatments, HCRU, and costs were reported. First-line therapy began upon first receipt of RT and/or temozolomide after index date; second-line therapy began when a new drug was added > 28 days after initiation of first-line therapy or when there was a treatment gap > 90 days. Treatment regimens, duration of treatment (corrected group prognosis method), HCRU, and costs were reported descriptively in the 0- to 6-month and 7- to 12-month periods following initiation of first-line and second-line therapy. RESULTS: Baseline characteristics were comparable between patients receiving temozolomide and/or RT. Patients receiving RT without chemotherapy tended to be older, be retired, and have more baseline comorbidities. Of the 4,071 patients receiving first-line therapy for GBM, most (73.0%) received temozolomide + RT; 24.4% received RT; and 2.5% received temozolomide monotherapy. Of those receiving first-line therapy, 1,283 (31.5%) patients subsequently received second-line therapy: 39.4% received bevacizumab monotherapy; 28.9% received bevacizumab combination therapy (temozolomide, 45.2% of patients; irinotecan, 24.3%; and temozolomide + lomustine, 15.4%); 15.5% received temozolomide monotherapy; and 13.7% received other systemic cancer therapies. The proportion of patients with hospitalizations increased from 2.9% (4-6 months pre-index) to 20.8% in the 3 months before the index date (likely due to diagnostic procedures) and 28.1% in the first 6 months after index (likely due to surgery) and then decreased to 13.3% in the 7- to 12-month period after index. Mean total per-patient costs at 6 and 12 months were $117,325 and $162,550 (first line) and $126,128 and $243,833 (second line). Costs in all time periods were largely driven by costs of RT/systemic cancer therapy. CONCLUSIONS: Most patients with newly diagnosed GBM received treatment according to recommendations. However, relatively few patients received second-line therapy, and the HCRU burden and costs associated with both lines of therapy were substantial. Novel therapies for GBM are required to improve treatment options and outcomes in these patients. DISCLOSURES: This study was funded by Bristol-Myers Squibb (Princeton Pike, NJ). Neither honoraria nor payments were provided for authorship. Norden received consultancy fees relating to this study from Bristol-Myers Squibb. Dastani, Korytowsky, Le, Singh, and You are employees of Bristol-Myers Squibb. Dastani and Korytowsky are shareholders of Bristol-Myers Squibb. Bobiak was an employee of Bristol-Myers Squibb at the time of this study. Preliminary data from this study were previously presented at the International Society for Pharmacoeconomics and Outcomes Research 22nd Annual International Meeting in Boston, MA, May 20-24, 2017.

Insurance correlates with improved access to care and outcome among glioblastoma patients.

Background: The current standard of care for glioblastoma (GBM) constitutes maximal safe surgical resection, followed by fractionated radiation and temozolomide. This treatment regimen is logistically burdensome, and in a health care system in which access to care is variable, there may be patients with worsened outcomes due to inadequate access to optimal treatment. Methods: The National Cancer Database was queried for patients with diagnoses of GBM in 2006-2014. Patients were grouped according to insurance status: private insurance, Medicare, Medicaid, or uninsured. Treatments provided (surgery, radiation, and chemotherapy) were compared between groups in univariate and multivariable logistic regression analysis. Results: A total of 61614 patients were analyzed. Compared with private insurance, the odds of surgery for Medicaid and uninsured patients were 0.72 (95% CI: 0.66-0.79) and 0.77 (95% CI: 0.69-0.87), respectively (P < 0.001). The multivariable odds of receiving radiotherapy were 0.91 (95% CI: 0.86-0.96), 0.62 (95% CI: 0.57-0.68), and 0.47 (95% CI: 0.43-0.52) for Medicare, Medicaid, and uninsured patients, respectively (all P < 0.001). In addition, the odds of receiving chemotherapy were 0.94 (95% CI: 0.89-0.99), 0.53 (95% CI: 0.49-0.57), and 0.41 (95% CI: 0.38-0.46) for Medicare, Medicaid, and uninsured patients, respectively (all P < 0.001). Conclusion: Insurance status and type of insurance coverage appear to impact treatments rendered for GBM, independently of other variables. Furthermore, we find that such differential access to care significantly impacts survival. Ensuring adequate access to care for all patients with diagnoses of glioblastoma is critical to optimize survival, especially as therapies continue to advance.

Disparities in health care determine prognosis in newly diagnosed glioblastoma.

OBJECTIVE Glioblastoma (GBM) is an aggressive brain malignancy with a short overall patient survival, yet there remains significant heterogeneity in outcomes. Although access to health care has previously been linked to impact on prognosis in several malignancies, this question remains incompletely answered in GBM. METHODS This study was a retrospective analysis of 354 newly diagnosed patients with GBM who underwent first resection at the authors' institution (2007-2015). RESULTS Of the 354 patients (median age 61 years, and 37.6% were females), 32 (9.0%) had no insurance, whereas 322 (91.0%) had insurance, of whom 131 (40.7%) had Medicare, 45 (14%) had Medicaid, and 146 (45.3%) had private insurance. On average, insured patients survived almost 2-fold longer (p < 0.0001) than those who were uninsured, whereas differences between specific insurance types did not influence survival. The adjusted hazard ratio (HR) for death was higher in uninsured patients (HR 2.27 [95% CI 1.49-3.33], p = 0.0003). Age, mean household income, tumor size at diagnosis, and extent of resection did not differ between insured and uninsured patients, but there was a disparity in primary care physician (PCP) status-none of the uninsured patients had PCPs, whereas 72% of insured patients had PCPs. Postoperative adjuvant treatment rates with temozolomide (TMZ) and radiation therapy (XRT) were significantly less in uninsured (TMZ in 56.3%, XRT in 56.3%) than in insured (TMZ in 75.2%, XRT in 79.2%; p = 0.02 and p = 0.003) patients. Insured patients receiving both agents had better prognosis than uninsured patients receiving the same treatment (9.1 vs 16.34 months; p = 0.025), suggesting that the survival effect in insured patients could only partly be explained by higher treatment rates. Moreover, having a PCP increased survival among the insured cohort (10.7 vs 16.1 months, HR 1.65 [95% CI 1.27-2.15]; p = 0.0001), which could be explained by significant differences in tumor diameter at initial diagnosis between patients with and without PCPs (4.3 vs 4.8 cm, p = 0.003), and a higher rate of clinical trial enrollment, suggesting a critical role of PCPs for a timelier diagnosis of GBM and proactive cancer care management. CONCLUSIONS Access to health care is a strong determinant of prognosis in newly diagnosed patients with GBM. Any type of insurance coverage and having a PCP improved prognosis in this patient cohort. Higher rates of treatment with TMZ plus XRT, clinical trial enrollment, fewer comorbidities, and early diagnosis may explain survival disparities. Lack of health insurance or a PCP are major challenges within the health care system, which, if improved upon, could favorably impact the prognosis of patients with GBM.

Costes indirectos asociados al glioblastoma. Experiencia en un centro / Indirect costs associated with glioblastoma: Experience at one hospital

Introducción: El glioblastoma es el tumor cerebral más frecuente. A pesar de los avances en su tratamiento, el pronóstico sigue siendo pobre, con una supervivencia media en torno a los 14 meses. Los costes directos, aquellos asociados al diagnóstico y el tratamiento de la enfermedad, han sido descritos ampliamente. Los costes indirectos, aquellos derivados de la pérdida de productividad debido a la enfermedad, han sido descritos en escasas ocasiones. Material y método: Realizamos un estudio retrospectivo, incluyendo a los pacientes diagnosticados entre el 1 de enero del 2010 y el 31 de diciembre del 2013 de glioblastoma en el Hospital Universitario Donostia. Recogimos datos demográficos, relativos al tratamiento ofertado y la supervivencia. Calculamos los costes indirectos a través del método del capital humano, obteniendo datos de sujetos comparables según sexo y edad, y de mortalidad de la población general a través del Instituto Nacional de Estadística. Los salarios pasados fueron actualizados a euros de 2015 según la tasa de inflación interanual y los salarios futuros fueron descontados en un 3,5% anual en forma de interés compuesto. Resultados: Revisamos a 99 pacientes, 46 mujeres (edad media 63,53 años) y 53 hombres (edad media 59,94 años). En 29 pacientes se realizó una biopsia y en los 70 restantes se realizó una cirugía resectiva. La supervivencia global media fue de 18,092 meses. Los costes indirectos totales fueron de 11.080.762 Euros (2015). El coste indirecto medio por paciente fue de 111.926 Euros (2015). Discusión: A pesar de que el glioblastoma es un tipo relativamente poco frecuente de tumor, que supone el 4% de todos los tipos de cáncer, su mal pronóstico y sus posibles secuelas generan una mortalidad y morbilidad desproporcionadamente altas. Esto se traduce en unos costes indirectos muy elevados. El clínico debe ser consciente del impacto del glioblastoma en la sociedad y los costes indirectos deben ser tenidos en cuenta en los estudios de coste-efectividad para conocer las consecuencias globales de esta enfermedad (AU)

Introduction: Glioblastoma is the most common primary brain tumour. Despite advances in treatment, its prognosis remains dismal, with a mean survival time of about 14 months. Many articles have addressed direct costs, those associated with the diagnosis and treatment of the disease. Indirect costs, those associated with loss of productivity due to the disease, have seldom been described. Material and method: We conducted a retrospective study in patients diagnosed with glioblastoma at Hospital Universitario Donostia between January 1, 2010 and December 31, 2013. We collected demographics, data regarding the treatment received, and survival times. We calculated the indirect costs with the human capital approach, adjusting the mean salaries of comparable individuals by sex and age and obtaining mortality data for the general population from the Spanish National Statistics Institute. Past salaries were updated to 2015 euros according to the annual inflation rate and we applied a discount of 3.5% compounded yearly to future salaries. Results: We reviewed the records of 99 patients: 46 women (mean age 63.53) and 53 men (mean age 59.94); 29 patients underwent a biopsy and the remaining 70 underwent excisional surgery. Mean survival was 18.092 months for the whole series. The total indirect cost for the series was Euros11 080 762 (2015). Mean indirect cost per patient was Euros 111 926 (2015). Discussion: Although glioblastoma is a relatively uncommon type of tumour, accounting for only 4% of all cancers, its poor prognosis and potential sequelae generate disproportionately large morbidity and mortality rates which translate to high indirect costs. Clinicians should be aware of the societal impact of glioblastoma and indirect costs should be taken into account when cost effectiveness studies are performed to better illustrate the overall consequences of this disease (AU)

Cost-effectiveness of the long-term use of temozolomide for treating newly diagnosed glioblastoma in Germany.

Concomitant radiochemotherapy followed by six cycles of temozolomide (= short term) is considered as standard therapy for adults with newly diagnosed glioblastoma. In contrast, open-end administration of temozolomide until progression (= long-term) is proposed by some authors as a viable alternative. We aimed to determine the cost-effectiveness of long-term temozolomide therapy for patients newly diagnosed with glioblastoma compared to standard therapy. A Markov model was constructed to compare medical costs and clinical outcomes for both therapy types over a time horizon of 60 months. Transition probabilities for standard therapy were calculated from randomized controlled trial data by Stupp et al. The data for long-term temozolomide therapy was collected by matching a cohort treated in the Department of Neurosurgery at Jena University Hospital. Health utilities were obtained from a previous cost utility study. The cost perspective was based on health insurance. The base case analysis showed a median overall survival of 17.1 months and a median progression-free survival of 7.4 months for patients in the long-term temozolomide therapy arm. The cost-effectiveness analysis using all base case parameters in a time-dependent Markov model resulted in an incremental effectiveness of 0.022 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was €351,909/QALY. Sensitivity analyses showed that parameters with the most influence on ICER were the health state utility of progression in both therapy arms. Although open-ended temozolomide therapy is very expensive, the ICER of this therapy is comparable to that of the standard temozolomide therapy for patients newly diagnosed with glioblastoma.

Newly diagnosed glioblastoma: adverse socioeconomic factors correlate with delay in radiotherapy initiation and worse overall survival.

The optimal time for starting radiation in patients with glioblastoma (GBM) is controversial. We aimed to evaluate postoperative radiotherapy treatment patterns and the impact of timing of radiotherapy on survival outcomes in patients with GBM using a large, national hospital-based registry in the era of Stupp chemoradiation. We performed a retrospective cohort study using the National Cancer Data Base and identified adults with GBM diagnosed between 2010 and 2013 and treated with chemoradiation. We classified time from surgery/biopsy to radiation start into the following categories: <15 days, 15-21 days, 22-28 days, 29-35 days, 36-42 days and >42 days. We assessed the relation between time to radiation start and survival using Cox proportional hazards modeling adjusting for clinically relevant variables that were selected a priori. We used multivariate logistic modeling to determine factors independently associated with receipt of delayed radiation treatment. A total of 12 738 patients met our inclusion criteria after our cohort selection process. The majority of patients underwent either gross total (n = 5270, 41%) or subtotal (n = 4700, 37%) resection, while 2768 patients (22%) underwent biopsy only. Median time from definitive surgery or biopsy to initiation of radiation was 29 days (interquartile range 24-36 days). For patients who had biopsy or subtotal resection, earlier initiation of radiation did not appear to be associated with improved survival. However, among patients who underwent gross total resection, there appeared to be improved survival with early initiation of radiation. Patients who initiated radiation within 15-21 days of gross total resection had improved survival (hazard ratio 0.82, 95% confidence interval 0.69-0.98, P = 0.03) compared with patients who had delayed (>42 days after surgery) radiation. There was also a trend (P = 0.07 to 0.12) for improved survival for patients who initiated radiation within 22-35 days of gross total resection compared with patients who had delayed radiation. Patients who were black, had Medicaid or other government insurance or were not insured, and who lived in metropolitan areas or further away from the treating facility had higher odds of receiving radiation >35 days after gross total resection. Patients who lived in higher income areas had higher odds of receiving radiation within 35 days of a gross total resection. In a large cohort of patients with GBM treated with chemoradiation, our data suggest a survival benefit in initiating radiotherapy within 35 days after gross total resection. Further research is warranted to understand barriers to timely access to optimal therapy.

Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail patients with glioblastoma.

BACKGROUND AND PURPOSE: Short-course radiotherapy (25 Gy in five fractions) was recently shown in a randomized phase III trial to be non-inferior to 40 Gy in 15 fractions in elderly and/or frail patients with glioblastoma multiforme. This study compared the cost-effectiveness of the two regimens. MATERIAL AND METHODS: The direct unit costs of imaging, radiotherapy (RT), and dexamethasone were collected from the five primary contributing countries to the trial, constituting the data of 88% of all patients. Effectiveness was measured by the restricted mean overall survival (RMOS) and progression free survival (RMPFS). The incremental cost-effectiveness ratio (ICER) was calculated. Indirect costs were also estimated for comparison. RESULTS: The median OSs for the short-course and commonly used RTs were 8.2 (95% confidence interval [CI] 6.1-10.3) and 7.7 (95% CI 5.5-9.9) months, respectively (log rank p = 0.340). Median PFSs were also not different (p = 0.686). The differences in the RMOS and the ICER, however, were +0.11 life-years and -$3062 United States dollars (USD) per life-year gained, respectively. The differences in the RMPFS and the ICER were +0.02 PFS and -$17,693 USD, respectively. CONCLUSION: The ICER of -$3062 per life-year gained and -$17,693 per PFS gained indicates that the short-course RT is less costly compared to the longer RT regimen.

Clinical and economic evaluation of modulated electrohyperthermia concurrent to dose-dense temozolomide 21/28 days regimen in the treatment of recurrent glioblastoma: a retrospective analysis of a two-centre German cohort trial with systematic comparison and effect-to-treatment analysis.

OBJECTIVE: To assess the efficacy and cost-effectiveness of modulated electrohyperthermia (mEHT) concurrent to dose-dense temozolomide (ddTMZ) 21/28 days regimen versus ddTMZ 21/28 days alone in patients with recurrent glioblastoma (GBM). DESIGN: A cohort of 54 patients with recurrent GBM treated with ddTMZ+mEHT in 2000-2005 was systematically retrospectively compared with five pooled ddTMZ 21/28 days cohorts (114 patients) enrolled in 2008-2013. RESULTS: The ddTMZ+mEHT cohort had a not significantly improved mean survival time (mST) versus the comparator (p=0.531) after a significantly less mean number of cycles (1.56 vs 3.98, p<0.001). Effect-to-treatment analysis (ETA) suggests that mEHT significantly enhances the efficacy of the ddTMZ 21/28 days regimen (p=0.011), with significantly less toxicity (no grade III-IV toxicity vs 45%-92%, p<0.0001). An estimated maximal attainable median survival time is 10.10 months (9.10-11.10). Cost-effectiveness analysis suggests that, unlike ddTMZ 21/28 days alone, ddTMZ+mEHT is cost-effective versus the applicable cost-effectiveness thresholds €US$25 000-50 000/quality-adjusted life year (QALY). Budget impact analysis suggests a significant saving of €8 577 947/$11 201 761 with 29.1-38.5 QALY gained per 1000 patients per year. Cost-benefit analysis suggests that mEHT is profitable and will generate revenues between €3 124 574 and $6 458 400, with a total economic effect (saving+revenues) of €5 700 034 to $8 237 432 per mEHT device over an 8-year period. CONCLUSIONS: Our ETA suggests that mEHT significantly improves survival of patients receiving the ddTMZ 21/28 days regimen. Economic evaluation suggests that ddTMZ+mEHT is cost-effective, budget-saving and profitable. After confirmation of the results, mEHT could be recommended for the treatment of recurrent GBM as a cost-effective enhancer of ddTMZ regimens, and, probably, of the regular 5/28 days regimen. mEHT is applicable also as a single treatment if chemotherapy is impossible, and as a salvage treatment after the failure of chemotherapy.

Hospitalizations in elderly glioblastoma patients.

BACKGROUND: Elderly glioblastoma (GB) patients are at risk of hospitalizations due to the morbidity of the disease and possible treatment toxicity. METHODS: In this observational cohort study, 255 newly diagnosed GB patients age 65 years and older were included. Survival, emergency room visits and admissions to an acute care hospital were determined. Mean and median total health care costs were calculated. Risk factors for Emergency room visits and acute care hospital admissions were determined. RESULTS: Median overall survival was 6 months. The majority of patients (68%) had at least one visit to the emergency department and 77% had at least one admission to acute care. The mean and median total costs (hospital, ambulatory, physician billing, other health care costs) per patient were $162,479.78 (CAN) and $125,511.00 (CAN), respectively. Treatment with radiation or treatment with radio-chemotherapy was associated with a relative risk (RR) of 2.31 (95% CI: 1.44-3.7; P=0.0005) and 2.19 (95% CI: 1.28-3.74; P=0.004), respectively for emergency department visits as compared to patients who were managed with comfort measures only. Patients with a baseline ECOG 0 had a RR of 1.71 (95% CI: 1.06-2.77; P=0.0289) and patients with baseline ECOG 1 had a RR of 1.49 (0.98-2.26; P=0.0623) for hospital admission as compared to patients with ECOG 4. CONCLUSIONS: A large proportion of elderly GB patients (particularly those with good baseline performance status who underwent active treatment) presented to the emergency department and had at least one admission to acute care.

Influence of insurance status on survival of adults with glioblastoma multiforme: A population-based study.

BACKGROUND: To the authors' knowledge, the impact of insurance status on the survival time of patients with glioblastoma multiforme (GBM) has not been fully understood. The objective of the current study was to clarify the association between insurance status and survival of patients with GBM by analyzing population-based data. METHODS: The authors performed a cohort study using data from the Surveillance, Epidemiology, and End Results program. They included adult patients (aged ≥18 years) with GBM as their primary diagnosis from the years 2007 to 2012. Patients without information regarding insurance status were excluded. A survival analysis between insurance status and GBM-related death was performed using an accelerated failure time model. Demographic and clinical variables were included to adjust for confounding effects. RESULTS: Among the 13,665 adult patients in the study cohort, 558 (4.1%) were uninsured, 1516 (11.1%) had Medicaid coverage, and 11,591 (84.8%) had non-Medicaid insurance. Compared with patients who were uninsured, insured patients were more likely to be older, female, white, married, and with a smaller tumor size at diagnosis. Accelerated failure time analysis demonstrated that older age (hazard ratio [HR], 1.04; P<.001), male sex (HR, 1.08; P<.001), large tumor size at the time of diagnosis (HR, 1.26; P<.001), uninsured status (HR, 1.14; P =.018), and Medicaid insurance (HR, 1.10; P =.006) were independent risk factors for shorter survival among patients with GBM, whereas radiotherapy (HR, 0.40; P<.001) and married status (HR, 0.86; P<.001) indicated a better outcome. The authors discovered an overall yearly progressive improvement in survival in patients with non-Medicaid insurance who were diagnosed from 2007 through 2011 (P =.015), but not in uninsured or Medicaid-insured patients. CONCLUSIONS: Variations existed in insurance status within the GBM population. Uninsured status and Medicaid insurance suggested shorter survival compared with non-Medicaid insurance among a population of patients with GBM. Cancer 2016;122:3157-65. © 2016 American Cancer Society.

The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma.

BACKGROUND: There is strong concern about the costs associated with adding tumor-treating fields (TTF) therapy to standard first-line treatment for glioblastoma (GBM). Hence, we aimed to determine the cost-effectiveness of TTF therapy for the treatment of newly diagnosed patients with GBM. METHODS: We developed a 3-health-state Markov model. The perspective was that of the French Health Insurance, and the horizon was lifetime. We calculated the transition probabilities from the survival parameters reported in the EF-14 trial. The main outcome measure was incremental effectiveness expressed as life-years gained (LYG). Input costs were derived from the literature. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/LYG. We used 1-way deterministic and probabilistic sensitivity analysis to evaluate the model uncertainty. RESULTS: In the base-case analysis, adding TTF therapy to standard of care resulted in increases of life expectancy of 4.08 months (0.34 LYG) and €185 476 per patient. The ICER was €549 909/LYG. The discounted ICER was €596 411/LYG. Parameters with the most influence on ICER were the cost of TTF therapy, followed equally by overall survival and progression-free survival in both arms. The probabilistic sensitivity analysis showed a 95% confidence interval of the ICER of €447 017/LYG to €745 805/LYG with 0% chance to be cost-effective at a threshold of €100 000/LYG. CONCLUSION: The ICER of TTF therapy at first-line treatment is far beyond conventional thresholds due to the prohibitive announced cost of the device. Strong price regulation by health authorities could make this technology more affordable and consequently accessible to patients.

Disparities in receipt of modern concurrent chemoradiotherapy in glioblastoma.

Temozolomide given concurrently with radiation after resection/biopsy improves survival in glioblastoma (GBM). The disparities in receipt of adjuvant single-agent chemotherapy and their association with outcome have not been well established. Observational study of a prospectively collected database, the National Cancer Database (NCDB), from 1998 to 2012 with median follow-up 12.4 months. Among the 114,979 patients in the NCDB with GBM, 44,531 patients were analyzed for disparities, and 28,279 patients were analyzed for overall survival (OS). Associations were assessed in a multivariable Cox proportional hazards regression model. Survival was estimated using the Kaplan-Meier method. Median age was 58 years. Chemotherapy use was associated with male gender, white race, younger age (≤50), higher performance status (≥70), more extensive surgery, insurance status, higher income/education, and treatment at academic centers (all p < 0.05). We found improved OS associated with type of insurance (private insurance HR 0.91, 95 % CI 0.85-0.96 and Medicare HR 1.24, 95 % CI 1.16-1.33, both p < 0.01 compared to uninsured) and treatment at academic programs (HR 0.86; p < 0.01). MGMT methylation status predicted improved OS (HR 0.54; 95 % CI 0.41-0.70, p < 0.01). 1-year OS for patients receiving chemotherapy was 55.9 % versus 35.3 % for those without (p < 0.0001). After adjustment for confounders, chemotherapy use remained associated with improved OS (HR 0.64, 95 % CI 0.63-0.66, p < 0.01). Chemotherapy utilization increased from 26.9 to 93.3 % during the study period. We have identified specific disparities in the use of chemotherapy that may be targeted to improve patient access to care. Widespread adoption of adjuvant chemoradiotherapy after resection or biopsy for GBM appears to improve OS.

Current trends in the management of glioblastoma in a French University Hospital and associated direct costs.

WHAT IS NEW AND OBJECTIVES: Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma (GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. METHODS: A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. RESULTS: Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5-ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). WHAT IS NEW AND CONCLUSION: This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours.

Economic Evaluation of Bevacizumab for the First-Line Treatment of Newly Diagnosed Glioblastoma Multiforme.

PURPOSE: The Avastin in Glioblastoma trial has shown that patients newly diagnosed with glioblastoma multiforme (GBM) treated with bevacizumab plus radiotherapy and temozolomide versus radiotherapy and temozolomide alone showed improvement in progression-free survival, possibly leading to a new indication for first-line use of bevacizumab in GBM. The cost-utility of this new intervention remains unknown; therefore, we developed a Markov model estimating the incremental cost-utility ratio (ICUR) from a Canadian public payer perspective. METHODS: We incorporated trial data for state transitions and treatment effects from the Avastin in Glioblastoma trial, costs and resource use data from Canadian published studies and databases, and utility parameters from published literature. We addressed uncertainty through one-way deterministic and probabilistic sensitivity analyses, extended the model to lifetime horizon and by another arm to compare first-line versus second-line use of bevacizumab on progression, performed value of information analysis, and performed US costing sensitivity analysis. RESULTS: Adding bevacizumab to radiotherapy and temozolomide resulted in increases of 0.13 quality-adjusted life-years (QALYs) and $80,000 per patient over 2-year time horizon at the base case analysis. The ICUR was $607,966/QALY (95% CI, $305,000/QALY to $2,550,000/QALY), with 0% chance of being cost effective at the $100,000/QALY willingness-to-pay threshold and never going below $450,000/QALY in the one-way sensitivity analysis. The ICUR using the US costing data was $787,519/QALY. The lifetime ICUR was $439,764/QALY (95% CI, $235,000/QALY to $1,520,000/QALY), never going below $350,000/QALY in the sensitivity analysis. Second-line use of bevacizumab on progression is more effective and less expensive than its first-line use. Value of information analysis revealed that future research is unwarranted. CONCLUSION: Bevacizumab has only limited effectiveness and is therefore not likely to be cost effective in treating adult patients with newly diagnosed GBM.

Socioeconomic status and glioblastoma risk: a population-based analysis.

PURPOSE: Socioeconomic status (SES) is associated with risk of various cancer types because of correlation between SES and causal factors or increased case ascertainment, or both. Studies evaluating the association between glioblastoma and occupational or SES factors have yielded inconsistent results. We evaluated the association between SES and glioblastoma risk using a large, population-based cancer registry dataset. METHODS: Data of the Surveillance, Epidemiology, and End Results Program were used to evaluate the impact of SES on glioblastoma risk. SES was divided into quintiles on the basis of census tract of residence. Census tracts are small, geographically defined areas with relatively homogeneous population characteristics. RESULTS: Higher SES was strongly associated with increased risk of glioblastoma (p < .001). Relative to persons living in census tracts of the lowest SES quintile, the highest SES quintile had a rate ratio of 1.45 (95 % CI 1.39-1.51) (p < .001). Similar associations were seen in population subgroups defined by age, sex, and race. CONCLUSIONS: The strong association between higher SES and greater glioblastoma risk is unlikely to represent an ascertainment effect because glioblastoma is rapidly progressive and ultimately fatal. A number of previously proposed glioma risk factors may be correlated with SES, including atopy and allergy rates, cellular telephone use, and body morphometric measures. Further research is needed to define the mechanism of this association.