Cost Of Bevacizumab Research Articles

Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.

Comparison of costs of bevacizumab, ranibizumab, and aflibercept in loading dose administration for diabetic macular edema treatment: Observational cost analysis

Comparison of costs of bevacizumab, ranibizumab, and aflibercept in loading dose administration for diabetic macular edema treatment: Observational cost analysis

Cost Effectiveness and Budget Impact of Nivolumab Plus Ipilimumab Versus Platinum Plus Pemetrexed (with and Without Bevacizumab) in Patients with Unresectable Malignant Pleural Mesothelioma in Switzerland.

Malignant pleural mesotheliomas (MPMs) are aggressive and often unresectable. In the past, chemotherapy was the standard for palliative treatment. However, immunotherapy with nivolumab+ipilimumab has recently received marketing approval. This study evaluated the cost effectiveness of nivolumab+ipilimumab versus pemetrexed+platinum (with/without bevacizumab) for Swiss patients with unresectable MPM, overall and by histological subtype. We developed a three-state Markov cohort model with a cycle length of 1month, a 30-year time horizon, and a discount rate of 3% per year for costs and benefits. The model included the updated survival and treatment-dependent utility results from the Checkmate-743 and MAPS registration trials. A Swiss statutory health insurance perspective was considered with unit costs for 2022 from publicly available and real-world sources. We assumed a willingness-to-pay (WTP) threshold of CHF100,000/QALY. Model robustness was explored in sensitivity and scenario analyses. Compared with chemotherapy, nivolumab+ipilimumab incurred additional costs of CHF109,115 and 0.57 additional quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of CHF192,585/QALY (i.e. USD201,829/QALY) gained. Relative to their 2022 list price, nivolumab+ipilimumab may be cost effective if priced at 48% across all histologies. Assuming cisplatin-based instead of carboplatin-based chemotherapy reduced the ICER to CHF158,911/QALY (i.e. USD166,539/QALY). For the non-epithelioid subtype, nivolumab+ipilimumab was cost effective compared with chemotherapy (ICER of CHF97,894/QALY, i.e. USD102,593/QALY). Chemotherapy+bevacizumab was often a dominated strategy or would require a bevacizumab cost reduction to 28%. Our model projected nivolumab+ipilimumab to be cost effective for the non-epithelioid subtype but not for all histologies. Substantial discounts for nivolumab+ipilimumab would be necessary to achieve cost effectiveness for all histologies.

Dose-dependent efficacy of bevacizumab in recurrent glioblastoma.

Bevacizumab (BEV), at a standard dose of 10mg/kg every 2weeks is associated with prolonged progression-free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). Few studies have examined the potential dose-dependent efficacy of BEV. In Ontario, reimbursement for the costs of BEV varies, and as a result, our practice began to routinely use lower dose regimens. The main aim of this study was to ensure that there was no harm to patients who received the low dose protocol. A single-center retrospective study of patients given BEV for rGBM between 2015 and 2020 was performed. Clinical and treatment data including BEV dose regimen [SD (10mg/kg every 2weeks) vs. LD (5mg/kg every 2-3weeks or 10mg/kg every 3weeks)] received at the time of rGBM diagnosis were captured. Overall survival (OS) and progression-free survival (PFS) on BEV were compared using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS. A total of 96 patients were included with a median follow-up duration of 6.84months (range 1.12-50.63 months) from the date of the first infusion. The LD group consisted of 55 of the 96 patients. By virtue of funding mechanisms for BEV, the median age in the LD group was significantly higher (62 vs. 54years p = 0.009). There was no difference in MGMT status between the two groups (p = 0.60). The LD group had prolonged median PFS (5.89months versus 3.22months; p = 0.0112) and OS (10.23months versus 6.28months; p = 0.0010). Multivariable analysis including the dose of BEV, the extent of resection, gender, and age revealed that standard dose of BEV, subtotal resection, and female sex were associated with worse overall survival. Nine patients in the SD group vs. 18 patients in the LD group reported an adverse event related to BEV. For patients with recurrent GBM, we found that a low dose regimen of BEV was associated with prolonged OS and PFS compared to the standard dose regimen. Lower dose schedules may be a better and more cost-effective option for patients with rGBM. Lower costs might provide more equitable access to this very important palliative drug.

QOL-25. IMPACTS OF IMPLEMENTING A PROSPECTIVE TREATMENT AND SURVEILLANCE PROTOCOL FOR THE MANAGEMENT OF NF2-ASSOCIATED VESTIBULAR SCHWANNOMAS ON TUMOR GROWTH, HEARING OUTCOMES, AND QUALITY OF LIFE

Abstract Neurofibromatosis type 2 (NF2) is an autosomal dominant neurocutaneous syndrome associated with the development of nervous system tumors, including vestibular schwannomas (VS), meningiomas, and ependymomas. Although considered a rare illness, it is a source of significant morbidity, mainly due to early hearing loss leading to decreased autonomy and productivity among young adults. Bevacizumab, a monoclonal antibody against VEGF, has been shown to improve audition and tumor size in observational studies on NF2-associated VS. The most common limitations in the literature include the lack of reliable control groups, the paucity of data on quality of life, and the lack of detailed audiology testing guidelines. Moreover, the cost of bevacizumab is a limiting factor in access to care. In our Canadian tertiary care center, bevacizumab has been offered to NF2 patients with VS complications without specific indications on optimal treatment initiation time or duration. We present a hybrid cohort study protocol with retrospective and prospective arms aimed at measuring the impacts of introducing a standardized treatment and surveillance protocol on tumor growth, hearing outcomes, and quality of life. Patients from the multidisciplinary neurofibromatosis clinic at the University of Montreal Health Center, Canada, will be evaluated for inclusion in the prospective arm through regular audiological evaluations and imaging. Eligible individuals will receive bevacizumab at an initial dose of 5 mg/kg every 2 weeks for a year while participating in serial audiological, radiological, and quality of life assessments. The results will be compared to those of our historical cohort. Our primary outcomes will be tumor growth rate (% per year) for vestibular schwannomas, meningiomas and ependymomas, audiological test results, and quality of life and subjective hearing estimated through standardized questionnaires (SF-36, SSQ). We hypothesize that patients enrolled in the prospective arm will show improved clinical response compared to our historical cohort.

Cost of Ranibizumab Port Delivery System vs Intravitreal Injections for Patients With Neovascular Age-Related Macular Degeneration

The study team investigated costs associated with the ranibizumab port delivery system (PDS) for neovascular age-related macular (nAMD), an alternative to conventional intravitreal anti-vascular endothelial growth factor (VEGF) injections. To investigate costs of intravitreal anti-VEGF injections vs ranibizumab PDS for patients with neovascular AMD (nAMD). This cost analysis used trial data and Medicare reimbursement rates and included patients with nAMD who were receiving ranibizumab, aflibercept, bevacizumab injections, or ranibizumab PDS. The number of intravitreal ranibizumab, aflibercept, and bevacizumab injections to break even with costs of ranibizumab PDS. Total direct medical costs over 1 year and 5 years for the ranibizumab PDS arm with refills at fixed 6-month intervals compared with monthly or bimonthly injections were calculated using Medicare rates. Scenario and sensitivity analyses accounted for uncertainty and variation. The mean (SD) number of ranibizumab, aflibercept, and bevacizumab injections to break even with the cost of ranibizumab PDS with 1 refill was 10.8 (1.3), 9.3 (1.1), and 34.5 (4.2), respectively. Ranibizumab PDS with fixed 6-month refills over 1 year cost $21 016 ($2102). Comparatively, monthly intravitreal ranibizumab cost $1943 (95% CI, -$3047 to $6932; P = .34) more, aflibercept cost $5702 (95% CI, $253-$11 151; P = .04) more, and bevacizumab cost $16 732 (95% CI, -$20 170 to -$13 294, P < .001) less. For bimonthly injections, aflibercept cost $7658 (95% CI, -$11 649.52 to -$3665.61; P = .006) less. Over 5 years, monthly intravitreal ranibizumab projected to cost $25 581 (95% CI, $2275-$48 887; P = .04) more, aflibercept cost $44 374 (95% CI, $18 623-$70 125; P = .008) more, and bevacizumab cost $67 793 (95% CI, -$82 501 to -$53 085; P < .001) less than PDS with fixed refills (mean [SD] cost, $89 218 [$8921]). For bimonthly injections, aflibercept cost $22 422 (95% CI, -$40 287 to -$45,56; P = .03) less. In scenario analyses, ranibizumab PDS with refills as needed offered cost savings compared with real-world intravitreal ranibizumab or aflibercept use at 5 years but not at 1 year. In this cost analysis, ranibizumab PDS with 1 refill cost more than intravitreal ranibizumab or aflibercept injections if less than or equal to approximately 11 or 10 injections, respectively, are required within the first year. Long term, if less than 4.4 and 3.8 injections are needed per refill, intravitreal ranibizumab and aflibercept is lower cost. Ranibizumab PDS costs more than intravitreal bevacizumab injections throughout scenarios.

Characterization of the Early Years of Bevacizumab Use for First-Line Treatment of Ovarian Cancer in the United States.

To quantify early dissemination patterns, factors influencing use, and costs of bevacizumab (BEV) for the treatment of newly diagnosed ovarian cancer (OC) in the United States before its regulatory approval for this indication (off-label use). We identified women 18-65 years of age with newly diagnosed OC treated with surgery and platinum-based chemotherapy from 2008 to 2016 through the MarketScan database (N = 8,109). The proportion of women receiving BEV over time was calculated, multivariate logistic regression used to determine factors associated with BEV use, and total costs per cycle of chemotherapy with and without BEV abstracted. BEV utilization rose 1.8-fold during the study period, from 4.1% (2008) to 7.4 % (2016). BEV was used with non-platinum/taxane regimens over a third of the time (37.2%). Physician specialty (medical oncology v gyn oncology) and geography (southeast region) were significantly associated with higher rates of use. Clinical factors associated with BEV use were metastatic disease and presence of ascites. The median cost of one cycle of platinum/taxane chemotherapy plus BEV was $10,897 in US dollars (USD) (interquartile range $7,573-$18,133 USD), compared with $1,629 USD (interquartile range, $683.0-$4,461 USD) for platinum/taxane alone. Off-label use of BEV for newly diagnosed OC was rare (< 10%), but doubled following presentation of phase II and III data at international meetings. Both clinical (ascites, metastatic disease, and age) and nonclinical (specialty and region) factors were associated with BEV use, and its use was accompanied by a six-fold increase in the cost of one cycle of treatment.

Economic Evaluation of Adding Bevacizumab to Chemotherapy for Metastatic Colorectal Cancer (mCRC) Patients in Indonesia.

Objective:Since 2016, bevacizumab has been widely used to treat metastatic colorectal cancer (mCRC) in Indonesia. Nevertheless, the high cost of bevacizumab has raised the question of whether the therapy is considered cost-effective and should be included in the national health insurance system. This study aimed to assess the cost-effectiveness of bevacizumab plus chemotherapy versus chemotherapy alone for the treatment of mCRC patients.Methods:A Markov model was applied using the perspective of the Indonesian healthcare system to assess cost-effectiveness. The health outcomes were expressed in terms of quality-adjusted life years (QALY) using the validated EuroQoL-5D-5L instrument. Data for medical costs were collected from hospital billings in four hospitals located in three different cities in Indonesia. Meanwhile, data for utility were obtained from interviewing 90 patients who came to the hospital. We compared those mCRC patients who received chemotherapy alone either with FOLFOX or FOLFIRI, versus patients who received the addition of bevacizumab. Results:With the perspective of societal, the incremental cost-effectiveness ratio (ICER) of adding bevacizumab was USD 49,312 per QALY gained using secondary data and USD 28,446 per QALY using real world data. Conclusion:Using either a healthcare or societal perspective, the addition of bevacizumab for mCRC treatment was considered not cost-effective.

Cost-effectiveness of cetuximab + FOLFIRI versus bevacizumab + FOLFIRI in the first-line treatment of RAS wild-type metastatic colorectal cancer in China.

133 Background: Adding cetuximab to FOLFIRI chemotherapy (cet+CT) as first-line (1L) treatment for RAS wild-type (wt) metastatic colorectal cancer (mCRC) has been reported as cost-effective vs bevacizumab + FOLFIRI (bev+CT) in multiple jurisdictions. This study determined the cost-effectiveness (CE) of cet+CT for patients with mCRC in China. Methods: A published 3–health-state (nonprogressive, progressive, death) CE model was adapted to reflect Chinese patient characteristics, health state utilities, unit costs, and discounting rates, applying FIRE-3 trial–based resource utilization and adverse event rates. Progression-free and overall survival estimates were based on published FIRE-3 trial simulations to statistically adjust for available later-line treatment modalities in China vs those observed in FIRE-3. [1] Cetuximab and bevacizumab costs were based on up-to-date prices after the 2019 national reimbursement drug listing negotiations. Incremental CE ratios (ICERs) are given as cost (Chinese Yuan [¥]) per life-year (LY) and quality-adjusted LY (QALY) gained. The willingness-to-pay (WTP) threshold was ¥193,931, equivalent to 3 times the gross domestic product per capita, following WHO guidance. Results: Overall costs/costs restricted to 1L treatment were ¥483,771/¥249,619 (cet+CT) and ¥366,036/¥156,802 (bev+CT). Health effects were 3.32/2.68 (cet+CT) and 2.39/1.94 (bev+CT) LYs/QALYs gained. Discounted ICERs for cet+CT vs bev+CT were ¥148,311 and ¥186,517 per LY and QALY gained in deterministic analysis. cet+CT had a 71.8% (LY) and 52.5% (QALY) probability of being cost-effective. Treatment duration with a biologic in 1L, utilities in 3L treatment, and duration of 2L treatment were the main outcome drivers. Conclusions: Projections suggest that cet+CT is cost-effective vs bev+CT for 1L treatment of patients with RAS wt mCRC in China, with ICERs below the current WTP threshold in deterministic and probabilistic sensitivity analyses. [1] Van Oostrum I, et al. Value Health. 2020;23(Suppl 1): S8.

Real-World Cost-Effectiveness of Bevacizumab With First-Line Combination Chemotherapy in Patients With Metastatic Colorectal Cancer: Population-Based Retrospective Cohort Studies in Three Canadian Provinces.

Background. Real-world evidence can be a valuable tool when clinical trial data are incomplete or uncertain. Bevacizumab was adopted as first-line therapy for metastatic colorectal cancer (mCRC) based on significant survival improvements in initial clinical trials; however, survival benefit diminished in subsequent analyses. Consequently, there is uncertainty surrounding the cost-effectiveness of bevacizumab therapy achieved in practice. Objective. To assess real-world cost-effectiveness of first-line bevacizumab with irinotecan-based chemotherapy versus irinotecan-based chemotherapy alone for mCRC in British Columbia (BC), Saskatchewan, and Ontario, Canada. Methods. Using provincial cancer registries and linked administrative databases, we identified mCRC patients who initiated publicly funded irinotecan-based chemotherapy, with or without bevacizumab, in 2000 to 2015. We compared bevacizumab-treated patients to historical controls (treated before bevacizumab funding) and contemporaneous controls (receiving chemotherapy without bevacizumab), using inverse-probability-of-treatment weighting with propensity scores to balance baseline covariates. We calculated incremental cost-effectiveness ratios (ICER) using 5-year cost and survival adjusted for censoring, with bootstrapping to characterize uncertainty. We also conducted one-way sensitivity analysis for key drivers of cost-effectiveness. Results. The cohorts included 12,112 (Ontario), 1,161 (Saskatchewan), and 2,977 (BC) patients. Bevacizumab significantly increased treatment costs, with mean ICERs between $78,000 and $84,000/LYG (life-year gained) in the contemporaneous comparisons and $75,000 and $101,000/LYG in the historical comparisons. Reducing the cost of bevacizumab by 50% brought ICERs in all comparisons below $61,000/LYG. Limitations. Residual confounding in observational data may bias results, while the use of original list prices overestimates current bevacizumab cost. Conclusion. The addition of bevacizumab to irinotecan-based chemotherapy extended survival for mCRC patients but at significant cost. At original list prices bevacizumab can only be considered cost-effective with certainty at a willingness-to-pay threshold over $100,000/LYG, but price reductions or discounts have a significant impact on cost-effectiveness.

Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis.

This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1‐ and 2‐year survival according to sex, age, co‐morbidities, management, population‐density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co‐morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One‐ and 2‐year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7–15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co‐morbidities, living in rural/semi‐rural area was associated with better 2‐year survival (HR: 0.83 [95% CI: 0.73–0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co‐morbidities, sex, age, and living place appear to be significant factors of prognosis.

Identifying factors to predict benefit from bevacizumab in progressive glioblastoma multiforme (GBM).

e13515 Background: Bevacizumab (BEV) has demonstrated activity in GBM, but the benefits have not been clearly defined in prospective randomised phase III trials. Some patients continue BEV for extended periods but little is known about predictors of clinical benefit. It has been suggested that a less intensive dose schedule might offer similar benefits. Methods: In a retrospective analysis of a National Neuro-Oncology centre database we examined biomarkers of BEV benefit on overall survival (OS), including age at diagnosis, time from diagnosis to BEV start, MGMT methylation and IDH-1 status. We compared those who derived clinical benefit (OS of ≥6-months) to those with limited clinical benefit (OS &lt;6 months). At our Institution, there is variable practice between Neuro-Oncologists in terms of BEV dose schedule. In this homogeneous patient population, we examined whether OS was similar for patients who received standard BEV dosing (10mg/kg q 2wks or 15mg/kg q 3wks) or reduced intensity BEV (5mg/kg q 2wks or 7.5mg/kg q 3wks). Results: Between January 1st 2010 and Dec 31st 2016, 170 patients received BEV for progressive GBM. Median OS was 5.5 months (Range: 0.5-54). OS was 42%, 18% and 2% at 6-, 12- and 24-months, respectively. No significant predictors of clinical benefit were identified (table). Importantly, median OS was similar for patients who received standard (N=94) vs. reduced intensity (N=76) BEV (5.2 vs. 5.6mo respectively), p=0.74. Conclusions: In this large cohort of patients, we did not identify predictors of benefit from BEV. OS was similar in patients who received standard or reduced intensity BEV. Given the cost of BEV, these results have important implications for value in cancer care. [Table: see text]

Benefits and costs of bevacizumab in recurrent glioblastoma: A quality adjusted survival and cost analysis (EVALUATE).

2032 Background: Routine clinical use of bevacizumab (Bev) in recurrent glioblastoma (rGBM) is controversial, as no large RCT has shown a survival advantage. We describe treatment algorithms, survival (OS), quality-adjusted survival (QAS) as well as costs of patients (pts) with GBM treated at an academic hospital in Switzerland, where Bev is registered and reimbursed for rGBM. Methods: Pts’ and treatment characteristics from diagnosis until death (including neurological symptoms and toxicities) of all pts over a 5-year period were retrospectively retrieved from our GBM database. For each treatment period (1st-line, recurrence and “best supportive care”) time to next treatment (TNT), OS and QAS were calculated and modelled for prognostic factors (Cox regression). QAS was evaluated as previously described (Murray et al). In- and out-patient costs were calculated from time of diagnosis until death in respect of Bev treatment (+Bev vs. –Bev). Results: 82 newly diagnosed GBM pts with a median age of 66 years (range 39-85), median KPS of 90% (range 50-100%), who were treated with 1 (n = 75), 2 (n = 36) or 3 (n = 14) lines of therapy, respectively, lived for a median OS of 11.9 (SD 9.7) months (mos). QAS was 5.3 (SD 6.9) mos i.e. 44% of the numerical survival time. 40% of patients were treated with Bev at 1st or 2nd recurrence. Pts, who were selected for BEV treatment, had a longer time from diagnosis to 2ndline treatment (median 5.2 (SD 6.3) mos) as compared to pts in the -Bev group (median 2.1 (SD 1.8) mos). Younger age and Bev treatment were associated with longer OS and QAS. QAS to OS ratio was 52% (9.4 out of 18.1 mos) for BEV treated patients and 34% (2.8 out of 8.2 mos) for the –Bev group, respectively. Bev treatment increased the overall treatment costs by 1.7x. The population adjusted incremental cost-effectiveness ratio (ICER) was CHF 75,669 per life year gained. Conclusions: QAS in patients with GBM is short (one third to half of OS). In our cohort, pts selected for Bev treatment had longer OS and longer QAS - at costs below the accepted threshold of 100,000 CHF per life year gained. Whether this gain of lifetime is a direct result of Bev treatment or a consequence of a selection bias needs to be addressed prospectively.

Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial

PurposeMalignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. MethodsTo estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. ResultsThe addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. ConclusionsThe combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population.

Bevacizumab in addition to chemotherapy first-line for right-side metastatic colorectal cancer: A cost-effectiveness analysis.

777 Background: To test the cost-effectiveness of bevacizumab treatment compared with cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for patients with right-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.232 QALYs with more $60,371 relative to bevacizumab therapy, resulting in an ICER of $259,775 /QALY. When PAP was available, the incremental cost decreased to $24,161, which yielded an ICER of $60,371 /QALY, which indicated that the strategy was not cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of bevacizumab was the most influential parameter. Conclusions: Bevacizumab treatment for right-side mCRC is not a cost-effective option in comparison with standard chemotherapy in Chinese context.

Cost-Effectiveness of Treatment Sequences of Chemotherapies and Targeted Biologics for Elderly Metastatic Colorectal Cancer Patients.

Treatment patterns for metastatic colorectal cancer (mCRC) patients have changed considerably over the last decade with the introduction of new chemotherapies and targeted biologics. These treatments are often administered in various sequences with limited evidence regarding their cost-effectiveness. To conduct a pharmacoeconomic evaluation of commonly administered treatment sequences among elderly mCRC patients. A probabilistic discrete event simulation model assuming Weibull distribution was developed to evaluate the cost-effectiveness of the following common treatment sequences: (a) first-line oxaliplatin/irinotecan followed by second-line oxaliplatin/irinotecan + bevacizumab (OI-OIB); (b) first-line oxaliplatin/irinotecan + bevacizumab followed by second-line oxaliplatin/irinotecan + bevacizumab (OIB-OIB); (c) OI-OIB followed by a third-line targeted biologic (OI-OIB-TB); and (d) OIB-OIB followed by a third-line targeted biologic (OIB-OIB-TB). Input parameters for the model were primarily obtained from the Surveillance, Epidemiology, and End Results-Medicare linked dataset for incident mCRC patients aged 65 years and older diagnosed from January 2004 through December 2009. A probabilistic sensitivity analysis was performed to account for parameter uncertainty. Costs (2014 U.S. dollars) and effectiveness were discounted at an annual rate of 3%. In the base case analyses, at the willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY) gained, the treatment sequence OIB-OIB (vs. OI-OIB) was not cost-effective with an incremental cost-effectiveness ratio (ICER) per patient of $119,007/QALY; OI-OIB-TB (vs. OIB-OIB) was dominated; and OIB-OIB-TB (vs. OIB-OIB) was not cost-effective with an ICER of $405,857/QALY. Results similar to the base case analysis were obtained assuming log-normal distribution. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $100,000/QALY gained, sequence OI-OIB was 34% cost-effective, followed by OIB-OIB (31%), OI-OIB-TB (20%), and OIB-OIB-TB (15%). Overall, survival increases marginally with the addition of targeted biologics, such as bevacizumab, at first line and third line at substantial costs. Treatment sequences with bevacizumab at first line and targeted biologics at third line may not be cost-effective at the commonly used threshold of $100,000/QALY gained, but a marginal decrease in the cost of bevacizumab may make treatment sequences with first-line bevacizumab cost-effective. Future economic evaluations should validate the study results using parameters from ongoing clinical trials. This study was supported in part by a grant from the Agency for Healthcare Research and Quality (R01-HS018956) and in part by a grant from the Cancer Prevention and Research Institute of Texas (RP130051), which were obtained by Du. The authors report no conflicts of interest. Study concept and design were primarily contributed by Parikh, along with the other authors. All authors participated in data collection, and Parikh took the lead in data interpretation and analysis, along with Lairson and Morgan, with assistance from Du. The manuscript was written primarily by Parikh, along with Lairson, Morgan, and Du, and revised by Parikh.

Treatment preferences of advanced ovarian cancer patients for adding bevacizumab to first-line therapy

BackgroundThe GOG-218 and ICON-7 studies recently showed that adding bevacizumab to first-line therapy for patients with advanced ovarian cancer increased progression-free survival. However, the high cost and long treatment duration prevents the incorporation of bevacizumab in practice. The aim of this study was to explore and quantify patients' preferences for adding bevacizumab to first-line therapy. MethodsA discrete choice experiment (DCE) and trade-off question were designed and distributed to 102 ovarian cancer patients. Participants were asked to choose between two hypothetical first-line therapies that differed in terms of effectiveness, safety, and the financial burden. A trade-off technique varying the cost of bevacizumab was used to quantify a willingness-to-pay threshold for selecting bevacizumab. ResultsAll attributes of the DCE had a statistically significant impact on respondents' preferences and the financial burden was the most important attribute. The results of the trade-off question showed that more than half of patients would prefer to add bevacizumab to standard chemotherapy when the cost of the drug was reduced to 17% (1/6) of the baseline cost. ConclusionPatients' preferences for bevacizumab in the adjuvant treatment of ovarian cancer depend primarily on drug costs. Our results suggest that the current cost of bevacizumab is sufficiently high that the majority of ovarian cancer patients are not willing to pay to accept a small increase in progression-free survival.

Bevacizumab cost effective in platinum-resistant ovarian cancer

Bevacizumab cost effective in platinum-resistant ovarian cancer

Is FDA-Approved Bevacizumab Cost-Effective When Included in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer?

Although the Food and Drug Administration has approved incorporation of bevacizumab (BEV) into the treatment of platinum-resistant ovarian cancer (PROC), cost-value measures are an essential consideration, as evidenced by the recent ASCO Value Framework initiative. We assessed the cost-effectiveness and reviewed the net health benefit (NHB) of this expensive treatment. A cost-effectiveness decision model was constructed using results from a phase III trial comparing BEV plus cytotoxic chemotherapy with chemotherapy alone in patients with PROC. The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial demonstrated improvement in progression-free survival and quality of life in patients receiving BEV. Costs, paracentesis rates, and adverse events were incorporated, including subgroup analysis of different partner chemotherapy agents. Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer meets the common willingness-to-pay incremental cost-effectiveness ratio (ICER) threshold of $100,000 per progression-free life-year saved (LYS) for 15-mg/kg dosing and approaches this threshold for 10-mg/kg dosing, with an ICER of $160,000. In sensitivity analysis, reducing the cost of BEV by 13% (from $9,338 to $8,100 per cycle) allows 10-mg/kg dosing to reach a $100,000 ICER. Exploratory analysis of different BEV chemotherapy partners showed an ICER of $76,000 per progression-free LYS (6.5-month progression-free survival improvement) and $54,000 per LYS (9.1-month overall survival improvement) for the addition of BEV to paclitaxel once per week. Using the ASCO framework for value assessment, the NHB score for BEV plus paclitaxel once per week is 48. Using a willingness-to-pay threshold of $100,000 ICER, the addition of BEV to chemotherapy either demonstrates or approaches cost-effectiveness and NHB when added to the treatment of patients with PROC.

A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN).

Bevacizumab (Avastin®, Roche), which is used in cancer therapy, is the 'parent' molecule from which ranibizumab (Lucentis®, Novartis) was derived for the treatment of neovascular age-related macular degeneration (nAMD). There were reports in the literature on the effectiveness of bevacizumab in treating nAMD, but no trials. The cost per dose of bevacizumab is about 5-10% that of ranibizumab. This trial was a head-to-head comparison of these two drugs. To compare the clinical effectiveness and cost-effectiveness of ranibizumab and bevacizumab, and two treatment regimens, for nAMD. Multicentre, factorial randomised controlled trial with within-trial cost-utility and cost-minimisation analyses from the perspective of the UK NHS. Participants, health professionals and researchers were masked to allocation of drug but not regimen. Computer-generated random allocations to combinations of ranibizumab or bevacizumab, and continuous or discontinuous regimen, were stratified by centre, blocked and concealed. Twenty-three ophthalmology departments in NHS hospitals. Patients ≥ 50 years old with active nAMD in the study eye with best corrected distance visual acuity (BCVA) ≥ 25 letters measured on a Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Previous treatment for nAMD, long-standing disease, lesion diameter > 6000 µm, thick blood at the fovea and any other confounding ocular disease were exclusion criteria. One eye per participant was studied; the fellow eye was treated according to usual care, if required. Ranibizumab and bevacizumab were procured commercially. Doses were ranibizumab 0.5 mg or bevacizumab 1.25 mg. The repackaged bevacizumab was quality assured. All participants were treated at visits 0, 1 and 2. Participants randomised to the continuous regimen were treated monthly thereafter. Participants randomised to the discontinuous regimen were not retreated after visit 2 unless pre-specified criteria for active disease were met. If retreatment was needed, monthly injections over 3 months were mandated. The primary outcome was BCVA. The non-inferiority margin was 3.5 letters. Secondary outcomes were contrast sensitivity; near visual acuity; reading index; neovascular lesion morphology; generic and disease-specific patient-reported outcomes, including macular disease-specific quality of life; survival free from treatment failure; resource use; quality-adjusted life-years (QALYs); and development of new geographic atrophy (GA) (outcome added during the trial). Results are reported for the study eye, except for patient-reported outcomes. Between 27 March 2008 and 15 October 2010, 610 participants were allocated and treated (314 ranibizumab, 296 bevacizumab; at 3 months, 305 continuous, 300 discontinuous). After 2 years, bevacizumab was neither non-inferior nor inferior to ranibizumab [-1.37 letters, 95% confidence interval (CI) -3.75 to +1.01 letters] and discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1.63 letters, 95% CI -4.01 to +0.75 letters). Lesion thickness at the fovea was similar by drug [geometric mean ratio (GMR) 0.96, 95% CI 0.90 to 1.03; p = 0.24] but 9% less with continuous treatment (GMR 0.91, 95% CI 0.85 to 0.97; p = 0.004). Odds of developing new GA during the trial were similar by drug [odds ratio (OR) 0.87, 95% CI 0.61 to 1.25; p = 0.46] but significantly higher with continuous treatment (OR 1.47, 95% CI 1.03 to 2.11; p = 0.033). Safety outcomes did not differ by drug but mortality was lower with continuous treatment (OR 0.47, 95% CI 0.22 to 1.03; p = 0.05). Continuous ranibizumab cost £3.5M per QALY compared with continuous bevacizumab; continuous bevacizumab cost £30,220 per QALY compared with discontinuous bevacizumab. These results were robust in sensitivity analyses. Ranibizumab and bevacizumab have similar efficacy. Discontinuing treatment and restarting when required results in slightly worse efficacy. Safety was worse with discontinuous treatment, although new GA developed more often with continuous treatment. Ranibizumab is not cost-effective, although it remains uncertain whether or not continuous bevacizumab is cost-effective compared with discontinuous bevacizumab at £20,000 per QALY threshold. Future studies should focus on the ocular safety of the two drugs, further optimisation of treatment regimens and criteria for stopping treatment. Current Controlled Trials ISRCTN92166560. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 78. See the NIHR Journals Library website for further project information.