Healthcare costs associated with bevacizumab and cetuximab in second-line treatment of metastatic colorectal cancer

Abstract

Objective:

To compare the health care costs of patients with metastatic colorectal cancer (mCRC) who received second-line treatment with Avastin (bevacizumab) versus Erbitux (cetuximab), from the third-party payer’s perspective.

Methods:

Patients with mCRC were selected from the PharMetrics claims database if they received second-line therapy containing either bevacizumab (second-line bevacizumab cohort) or cetuximab (second-line cetuximab cohort). Six-month costs following second-line therapy start date and average monthly healthcare costs while on second-line therapy (in 2009 US$) were calculated and compared between the two groups.

Results:

A total of 2188 patients with mCRC who met the eligibility criteria were included in the analysis, including 1808 patients receiving bevacizumab and 380 patients receiving cetuximab in second-line treatment. Demographic and baseline characteristics were similar between the two groups. Patients’ mean age was 61 years and 56% were males. In second-line treatment, bevacizumab was commonly used with oxaliplatin (43.5%) and irinotecan-based regimens (40.4%), whereas cetuximab was commonly used with irinotecan-based regimens (68.2%). Bevacizumab patients had significantly lower total all-cause healthcare costs than cetuximab patients (adjusted difference: –$10,231, p?=?0.020), and lower medical costs (–$10,796, p?=?0.012) during the 6 months following second-line therapy initiation. Approximately half of the difference in total all-cause healthcare costs was attributable to the lower chemotherapy and targeted therapy costs (–$5635, p?=?0.032) of bevacizumab patients than those of cetuximab patients. While on second-line therapy, bevacizumab patients also had lower average monthly all-cause healthcare costs than cetuximab patients.

Limitations:

Second-line treatment in the current study was defined based on changes in mCRC medications, not based on disease progression due to the limited clinical information available in claims.

Conclusion:

The use of bevacizumab in second-line therapy was associated with significantly lower healthcare costs in mCRC patients, compared to the use of cetuximab.     

Cost-minimization analysis of panitumumab compared with cetuximab for first-line treatment of patients with wild-type RAS metastatic colorectal cancer

Abstract

Objective:

To compare the costs of first-line treatment with panitumumab?+?FOLFOX in comparison to cetuximab?+?FOLFIRI among patients with wild-type (WT) RAS metastatic colorectal cancer (mCRC) in the US.     

A within-trial cost-effectiveness analysis of panitumumab compared with bevacizumab in the first-line treatment of patients with wild-type RAS metastatic colorectal cancer in the US

Abstract

Aims: This analysis investigated the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) compared with bevacizumab plus mFOLFOX6 in the first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC).

Materials and methods: The cost-effectiveness analysis was developed from a third-party payer perspective in the US and was implemented using a partitioned survival model with health states for first-line treatment (progression-free), disease progression with and without subsequent active treatment, and death. Survival analyses of patients with wild-type RAS mCRC from the PEAK head-to-head clinical trial of panitumumab vs bevacizumab were performed to estimate time in the model health states. Additional data from PEAK informed the amount of each drug consumed, duration of therapy, subsequent therapy use, and toxicities related to mCRC treatment. Literature and US public data sources were used to estimate unit costs associated with treatment and duration of subsequent active therapies. Utility weights were calculated from patient-level data from panitumumab trials in the first-, second-, and third-line settings. A life-time perspective was taken with future costs and outcomes discounted at 3% per annum. Scenario, one-way, and probabilistic sensitivity analyses were performed.

Results: Compared with bevacizumab, the use of panitumumab resulted in an incremental cost of US $60,286, and an incremental quality-adjusted life-year (QALY) of 0.445, translating into a cost per QALY gained of US $135,391 in favor of panitumumab. Results were sensitive to wastage and dose rounding assumptions modeled.

Limitations: Progression-free and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves. Costs and quality of life were estimated from multiple and different data sources.

Conclusions: The efficacy of panitumumab in extending progression-free and overall survival and improving quality of life makes it a cost-effective option for first-line treatment of patients with wild-type RAS mCRC compared with bevacizumab.     

Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer

Objective: To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain.

Methods: A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model.

Results: Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions.

Limitations: The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously.

Conclusions: Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab?+?mFOLFOX6 could be considered a cost-effective option compared with bevacizumab?+?mFOLFOX6 for the Spanish NHS.     

Corroboration of claims algorithm for second-line costs of metastatic colorectal cancer treatment with targeted agents

Abstract

Objective:

To refine a claims algorithm for identifying second-line systemic regimens for metastatic colorectal cancer (mCRC) based on clinical evidence and to compare costs during second-line treatment by targeted therapy administered.

Methods:

This retrospective analysis of a large US managed care database identified patients diagnosed with mCRC during 1 July 2007–30 June 2011. A claims-based algorithm was developed to identify patients with at least two lines of therapy (LOT) and the second LOT contained one targeted agent: bevacizumab or any anti-epidermal growth factor receptor (EGFR). Medical chart data from 92 patients were used to corroborate and refine the LOT algorithm. The positive predictive value (PPV) of the initial algorithm and refined algorithm for identification of second LOT are presented. The final algorithm was applied to claims data and two mutually exclusive second-line cohorts were examined: patients with bevacizumab- or cetuximab-containing regimens. Second-line healthcare costs were analyzed with generalized linear models adjusted for demographic and clinical characteristics.

Results:

The PPV increased from 50.0% (95% CI?=?39.4–60.6) for the initial algorithm to 72.1% (95% CI?=?59.2–82.9) for the final algorithm. Mean age in the cohorts (n?=?569) was 61 years; 58% were men. Days of therapy were similar for the bevacizumab (n?=?450) vs cetuximab (n?=?119) cohorts, respectively: 131 vs 148 in first LOT and 123 (both cohorts) in second LOT (p?≥?0.27). Total costs during second-line treatment in the bevacizumab cohort were lower by $12,318 (p?=?0.02) and medical costs were lower by $13,809 (p?=?0.01). Monthly total and medical costs were lower by $2728 (p?=?0.03) and $3133 (p?=?0.01), respectively. Results are based on commercially or Medicare-insured patients and may not be generalizable to Medicaid or uninsured patients.

Conclusions:

Corroboration of claim-based algorithms with medical chart data improved algorithm performance. Second-line total and medical costs were lower for mCRC patients treated with bevacizumab compared with cetuximab.     

The economic burden of common adverse events associated with metastatic colorectal cancer treatment in the United States

Aims: Adverse events (AEs) associated with treatments for metastatic colorectal cancer (mCRC) may compromise the course of treatment, impact quality-of-life, and increase healthcare resource utilization. This study assessed the direct healthcare costs of common AEs among mCRC patients in the US.

Methods: Adult mCRC patients treated with chemotherapy or targeted therapies were identified from administrative claims databases (2009–2014). Up to the first three mCRC treatment episodes per patient were considered and categorized as with or without the AE system/organ category during the episode. Total healthcare costs (2014 USD) were measured by treatment episode and reported on a monthly basis. Treatment episodes with the AE category were matched by treatment type and line of treatment to those without the AE category. Adjusted total cost differences were estimated by comparing costs during treatment episodes with vs without the AE category using multivariate regression models; p-values were estimated with bootstrap.

Results: A total of 4158 patients with ≥1 mCRC treatment episode were included (mean age?=?59 years; 58% male; 60% with liver and 14% with lung metastases; 2,261 [54%] with a second and 1,115 [27%] with a third episode). On average, two treatment episodes were observed per patient with an average length of 166 days per episode. Adjusted monthly total cost difference by AE category included hematologic ($1,480), respiratory ($1,253), endocrine/metabolic ($1,213), central nervous system (CNS; $1,136), and cardiovascular ($1,036; all p?Limitations: Claims do not include information on the cause of AEs, and potentially less severe AEs may not have been reported by the physician when billing the medical service. This study aimed to assess the association between costs and AEs and not the causation of AEs by treatment.

Conclusions: The most costly AEs among mCRC patients were hematologic, followed by respiratory, endocrine/metabolic, CNS, and cardiovascular.     

Costs of hospital events in patients with metastatic colorectal cancer

Abstract

Background:

In the last decade, the number of new agents, including monoclonal antibodies, being developed to treat metastatic colorectal cancer (mCRC) increased rapidly. While improving outcomes, these new treatments also have distinct and known safety profiles with toxicities that may require hospitalizations. However, patterns and costs of hospitalizations of toxicities of these new ‘targeted’ drugs are often unknown.

Objective:

This study aimed to estimate the costs of hospital events associated with adverse events specified in the ‘Special Warnings and Precautions for Use’ section of the European Medicinal Agency Summary of Product Characteristics for bevacizumab, cetuximab, and panitumumab, in patients with mCRC.

Methods:

From the PHARMO Record Linkage System (RLS), patients with a primary or secondary hospital discharge code for CRC and distant metastasis between 2000–2008 were selected and defined as patients with mCRC. The first discharge diagnosis defining metastases served as the index date. Patients were followed from index date until end of data collection, death, or end of study period, whichever occurred first. Hospital events during follow-up were identified through primary hospital discharge codes. Main outcomes for each event were length of stay and costs per hospital admission.

Results:

Among 2964 mCRC patients, 271 hospital events occurred in 210 patients (mean [SD] duration of follow-up: 34 [31] months). The longest mean (SD) length of stay per hospital admission were for stroke (16 [33] days), arterial thromboembolism (ATE) (14 [21] days), wound-healing complications (WHC), acute myocardial infarction (AMI), congestive heart failure (CHF), and neutropenia (all 9 days; SD 5–15). Highest mean (SD) costs per admission were for stroke (€13,500 [€28,800]), ATE (€13,300 [€18,800]), WHC (€10,800 [€20,500]).

Limitations:

Although no causal link could be identified between any specific event and any specific treatment, data from this study are valuable for pharmacoeconomic evaluations of newer treatments in mCRC patients.

Conclusions:

Inpatient costs for events in mCRC patients are considerable and vary greatly.     

手术治疗急性梗阻性大肠癌临床探讨(附168例报告)

目的 探讨急性梗阻性大肠癌的手术治疗原则及预后.方法 分析168 例急性梗阻性大肠癌的手术治疗临床资料,其中右半结肠癌18 例,左半结肠癌60 例,直肠癌90 例.168 例中Dukes B 期24 例,C期80例,D期64 例.168 例均手术治疗,其中行结肠造口18 例,miles 手术64 例,Hartmann 手术18 例,一期切除吻合加肠外置术12 例,结肠灌洗一期切除吻合56 例.结果 治愈164 例,死亡4 例.未能切除癌肿的2 例患者术后5 月死亡.结论 手术治疗是解除急性梗阻性大肠癌的唯一方法.应根据患者的不同情况选择合理的手术方式.     

Comparative net cost impact of the utilization of panitumumab versus cetuximab for the treatment of patients with metastatic colorectal cancer in Canada

Objective:

Clinical practice guidelines support the use of the epidermal growth factor receptor (EGFR) inhibitors panitumumab and cetuximab for the treatment of metastatic colorectal cancer (mCRC) after failure of other chemotherapy regimens, based on significant clinical benefits in patients with wild-type KRAS. The purpose of the analysis was to compare provincial hospital costs when using panitumumab vs cetuximab with or without irinotecan in this patient population using a Net Impact Analysis (NIA) approach.

Methods:

The NIA determined the total per patient cost of the reimbursed regimens of panitumumab vs cetuximab in British Columbia, Alberta, Manitoba, Ontario, and Québec. Utilization of healthcare resources related to EGFR inhibitor infusions, follow-up monitoring, and treatment of adverse events (AEs) were also included. Healthcare resource use including drugs, medical supplies, laboratory testing, oncology infusion time, and healthcare professionals’ time was obtained through expert consultation and the use was then multiplied by the province-specific cost of each resource. Numerous sensitivity analyses were conducted.

Results:

Based on the dosing regimens in place in each province, the total annual per patient cost of panitumumab ranged from $22,203–$32,600, while the total annual per patient cost of cetuximab treatment varied from $30,321–$40,908. Treatment with panitumumab resulted in lower costs in all cost categories including drug acquisition, infusion preparation/administration, patient monitoring, and AE management. Per patient savings with panitumumab ranged from a low of $3815 in British Columbia to a high of $10,603 in Ontario. In sensitivity analyses, panitumumab remained cost saving in all scenarios where the savings ranged from $150–$16,006 per patient.

Conclusions:

Treating chemorefractory mCRC patients with panitumumab rather than cetuximab reduced healthcare resource costs. Provincial healthcare savings achieved with the use of panitumumab could potentially be re-allocated to other cancer treatments, although further study would be needed to validate this assumption.     

Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive,non-small cell lung cancer in China

Purpose: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China.

Methods: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model.

Results: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1?mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY.

Conclusions: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.     

Medical resource use and cost of different first-line treatments for metastatic colorectal cancer in Brazil

Abstract

Background: Metastatic colorectal cancer (mCRC) is one of the most common malignancies worldwide. The availability of new chemotherapeutic agents have modified the treatment of mCRC over the years creating the need to evaluate the financial impact of treatment. The aim of this study was to establish and quantify the financial resources needed during the first-line treatment of mCRC in Brazil.

Methods: The authors began by reaching expert consensus using a modified Delphi panel with oncologists working at public and private services in Brazil. Costs were calculated using official databases and the microcosting technique.

Results: The panel reached consensus on six regimens used in the first-line treatment of mCRC, as well as the resources involved in the administration of these regimens. All the regimens contain either fluorouracil (5-FU)/leucovorin or capecitabine, combined with either oxaliplatin or irinotecan. The analysis showed that, when compared with intravenous 5-FU/leucovorin, the cost of capecitabine was offset by administration costs.

Conclusion: The panel concluded that regimens containing capecitabine, especially capecitabine plus oxaliplatin (XELOX) are less expensive than those containing 5-FU/leucovorin. Given the comparable efficacy and good tolerability of the XELOX regimen, it may be an attractive choice for the first-line treatment of Brazilian patients with mCRC.     

Economic evaluation for the US of nab-paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer

Background: Nab-paclitaxel plus gemcitabine (NAB-P?+?GEM) and FOLFIRINOX have shown superior efficacy over gemcitabine (GEM) in the treatment of metastatic pancreatic ductal adenocarcinoma (mPDA). Although the incremental clinical benefits are modest, both treatments represent significant advances in the treatment of a high-mortality cancer. In this independent economic evaluation for the US, the aim was to estimate the comparative cost-utility and cost-effectiveness of these three regimens from the payer perspective.

Methods: In the absence of a direct treatment comparison in a single clinical trial, the Bucher indirect comparison method was used to estimate the comparative efficacy of each regimen. A Markov model evaluated life years (LY) and quality-adjusted life years (QALY) gained with NAB-P?+?GEM and FOLFIRINOX over GEM, expressed as incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). All costs and outcomes were discounted at 3%/year. The impact of parameter uncertainty on the model was assessed by probabilistic sensitivity analyses.

Results: NAB-P?+?GEM was associated with differentials of +0.180 LY and +0.127 QALY gained over GEM at an incremental total cost of $25,965; yielding an ICER of $144,096/LY and ICUR of $204,369/QALY gained. FOLFIRINOX was associated with differentials of +0.368 LY and +0.249 QALY gained over GEM at an incremental total cost of $93,045; yielding an ICER of $253,162/LY and ICUR of $372,813/QALY gained. In indirect comparison, the overall survival hazard ratio (OS HR) for NAB-P?+?GEM vs FOLFIRINOX was 0.79 (95%CI?=?0.59–1.05), indicating no superiority in OS of either regimen. FOLFIRINOX had an ICER of $358,067/LY and an ICUR of $547,480/QALY gained over NAB-P?+?GEM. Tornado diagrams identified variation in the OS HR, but no other parameters, to impact the NAB-P?+?GEM and FOLFIRINOX ICURs.

Conclusions: In the absence of a statistically significant difference in OS between NAB-P?+?GEM and FOLFIRINOX, this US analysis indicates that the greater economic benefit in terms of cost-savings and incremental cost-effectiveness and cost-utility ratios favors NAB-P?+?GEM over FOLFIRINOX.     

Retrospective analysis of patients with advanced or metastatic gastric cancer in Colombia

Abstract

Aims: To assess patient and disease characteristics, treatment patterns, and associated costs in patients with advanced or metastatic gastric cancer (A/MGC) in Colombia, in both the public and private hospitals.

Materials and methods: A total of 145 patients who had received first-line chemotherapy treatment (platinum analog and/or a fluoropyrimidine) and were followed for at least 3 months after the last administration of a first-line cytotoxic agent were eligible for inclusion. Case-report forms were elaborated based on the patients’ medical records from three Colombian hospitals. Estimates of treatment costs were calculated using unit costs from the participating hospitals.

Results: Of the 145 patients, more than half (64.83%) were male, 79.56% were diagnosed with metastatic stage IV disease (mean age = 58.14?years). Prior to MGC diagnosis, 31.71% of the patients being operated on received a total gastrectomy; 66.9% of the patients received a doublet therapy, of which 5-fluorouracil (5-FU) in combination with cisplatin was the standard treatment (14%), followed by combination with leucovorin (12%). Only around 10% of the patients responded to first-line treatment. Out of 41.38% of the patients who received a second-line treatment, 71.67% were still administered a platinum analog and/or fluoropyrimidine. During the follow-up period, 52% of the patients progressed and 20% achieved stable disease. Best supportive care mostly consisted of outpatient visits after last line-therapy (72.41%), palliative radiotherapy (18.6%), and surgery (37.2%).

Limitations and conclusions: Gastric cancer is one of the main causes of cancer-related death in Colombia, as most of the patients are diagnosed at an advanced stage, when prognosis is poor. Treatment patterns are highly heterogeneous. Second-line treatments were mostly initiated with paclitaxel, capecitabine, irinotecan, or cisplatin.     

Cost per median overall survival month associated with abiraterone acetate and enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer

Objective: To calculate costs per median overall survival (OS) month in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate plus prednisone (AA?+?P) or enzalutamide. Methods: Median treatment duration and median OS data from published Phase 3 clinical trials and prescribing information were used to calculate costs per median OS month based on wholesale acquisition costs (WACs) for patients with mCRPC treated with AA?+?P or enzalutamide. Sensitivity analyses were performed to understand how variations in treatment duration and treatment-related monitoring recommendations influenced cost per median OS month. Cost-effectiveness estimates of other Phase 3 trial outcomes were also explored: cost per month of chemotherapy avoided and per median radiographic progression-free survival (rPFS) month. Results: The results demonstrated that AA?+?P has a lower cost per median OS month than enzalutamide ($3231 vs 4512; 28% reduction), based on the following assumptions: median treatment duration of 14 months for AA?+?P and 18 months for enzalutamide, median OS of 34.7 months for AA?+?P and 35.3 months for enzalutamide, and WAC per 30-day supply of $8007.17 for AA?+?P vs $8847.98 for enzalutamide. Sensitivity analyses showed that accounting for recommended treatment-related monitoring costs or assuming identical treatment durations for AA?+?P and enzalutamide (18 months) resulted in costs per median OS month 8–27% lower for AA?+?P than for enzalutamide. Costs per month of chemotherapy avoided were $4448 for AA?+?P and $5688 for enzalutamide, while costs per month to achieve median rPFS were $6794 for AA?+?P and $7963 for enzalutamide. Conclusions: This cost-effectiveness analysis demonstrated that costs per median OS month, along with costs of other Phase 3 trial outcomes, were lower for AA?+?P than for enzalutamide. The findings were robust to sensitivity analyses. These results have important implications for population health decision-makers evaluating the relative value of therapies for mCRPC patients.     

Cost drivers for breast,lung, and colorectal cancer care in a commercially insured population over a 6-month episode: an economic analysis from a health plan perspective

Aims: In the absence of clinical data, accurate identification of cost drivers is needed for economic comparison in an alternate payment model. From a health plan perspective using claims data in a commercial population, the objective was to identify and quantify the effects of cost drivers in economic models of breast, lung, and colorectal cancer costs over a 6-month episode following initial chemotherapy.

Research design and methods: This study analyzed claims data from 9,748 Cigna beneficiaries with diagnosis of breast, lung, and colorectal cancer following initial chemotherapy from January 1, 2014 to December 31, 2015. We used multivariable regression models to quantify the impact of key factors on cost during the initial 6-month cancer care episode.

Results: Metastasis, facility provider affiliation, episode risk group (ERG) risk score, and radiation were cost drivers for all three types of cancer (breast, lung, and colorectal). In addition, younger age (p?p?p?p?p?Conclusions: Value-based reimbursement models in oncology should appropriately account for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, this study recommends adjusting for the factors identified in these models to predict costs in breast, lung, and colorectal cancers.     

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

Objective:

Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE?+?EXE). This study estimates the costs of managing adverse events (AEs) during EVE?+?EXE therapy and single-agent chemotherapy in Western Europe.

Methods:

An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE?+?EXE or chemotherapies. AE rates for patients receiving EVE?+?EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€).

Results:

The EVE?+?EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE?+?EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively.

Conclusions:

The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE?+?EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.     

Cost-effectiveness analysis of sequential biologic therapy with ixekizumab versus secukinumab as first-line treatment of moderate-to-severe psoriasis in the UK

Aims: Patients with psoriasis often undergo treatment with a sequence of biologic agents because of poor/loss of response to initial therapy. With the availability of newer agents like ixekizumab and secukinumab, there is a need for cost-effectiveness analyses to better reflect current clinical practice. This study aimed to assess the cost-effectiveness of a sequence of biologic therapies containing first-line ixekizumab vs first-line secukinumab in patients with moderate-to-severe plaque psoriasis in the UK.

Materials and methods: A Markov model with a lifetime horizon was developed to compare the cost-effectiveness of ixekizumab and secukinumab treatment sequences: ixekizumab → ustekinumab → infliximab → best supportive care (BSC) vs secukinumab → ustekinumab → infliximab → BSC. The model used monthly cycles, and included four health states: trial period, treatment maintenance, BSC, and death. At the end of the trial period, responders transitioned to maintenance therapy; non-responders transitioned to the next biologic in the sequence. An annual discontinuation rate of 20% was assumed for maintenance therapy.

Results: The ixekizumab sequence provided cost savings of £898 (£176,203 vs 177,101) [year 2015 values] and gained 0.03 more quality-adjusted life-years (QALYs: 1.45 vs 1.42) vs the secukinumab sequence over the lifetime horizon. Probabilistic sensitivity analysis showed an 89.8% likelihood that the ixekizumab sequence would be cost-effective at a threshold of £20,000 per QALY gained.

Limitations: The analysis used list prices for drugs rather than confidential, preferentially priced Patient Access Scheme costs. In addition, efficacy input data were based on a network meta-analysis, as there were no head-to-head trials comparing ixekizumab and secukinumab.

Conclusion: First-line treatment with ixekizumab as part of a specific sequential biologic therapy for moderate-to-severe plaque psoriasis in the UK provided slight advantages in cost savings and QALYs gained over a similar treatment sequence initiated with secukinumab. In view of the small magnitude of these differences, factors such as patient preferences (e.g. for number of injections) and long-term safety (e.g. related to time on the market) may also be important for clinical decision-making.     

An economic comparison of the net clinical benefit and treatment costs of raltitrexed and 5-fluorouracil + leucovorin (Mayo regimen) in advanced colorectal cancer

Summary

Background

This paper describes an economic evaluation in which raltitrexed (Tomudex®) was compared with 5-fluorouracil (5-FU) + leucovorin (LV), and where net clinical benefits were related to differential health service costs. Raltitrexed, a specific inhibitor of thymidylate synthetase, has shown anticancer activity against a range of solid tumours.

Tomudex® is a registered trademark ofZeneca Pharmaceuticals

Materials and Methods

In a large, open, randomised, multicentre study in patients with advanced colorectal cancer, raltitrexed (n = 223) and 5-FU plus LV (n = 216) showed similar efficacy in terms of patient survival and objective response (i.e. tumour shrinkage rates). Palliative benefits were seen in both groups of patients and suggest that patients with stable disease are as likely to show improvement as those with a tumour response. Reductions compared with 5-FU plus LV in the number of toxicity days (median 1.5 vs 8 treatment days) and administration days (6 vs 22 days) with raltitrexed were consistent with a net clinical benefit.

Results

A cost minimisation analysis that drew on data from a number of sources showed direct medical costs per month to be similar for the two treatments (£781 for raltitrexed vs £834 for 5-FU + LV).

Conclusions

Raltitrexed therefore represents a clinically effective alternative to 5-FU plus LV (Mayo regimen) and offers net clinical benefit to patients with advanced colorectal cancer at no apparent additional cost.