Cost-Effectiveness Analysis of FOLFIRI-Based First-Line Regimens for Metastatic Colorectal Cancer Using Clinical Decision Analysis.

OBJECTIVE: Metastatic colorectal cancer with KRAS wild type is treated using a range of drug regimens, including fluorouracil, irinotecan, and Leucovorin(FOLFIRI)plus bevacizumab(Bmab), cetuximab(Cmab), or panitumumab(Pmab). The present study aimed to identify the optimal regimen using a decision analysis method, in combination with clinical and economic evidence. METHOD: A simple Markov model with a monthly cycle time was constructed. Probabilistic variables for input into the model were derived from randomized controlled trials. Direct costs for the drugs, laboratory analyses, and medical staff were calculated and used in the model. RESULTS: The expected survival times and costs of FOLFIRI alone and combination therapies were 20.9 months and 2,299,198 yen for FOLFIRI, 29.9 months and 8,929,888 yen for Bmab, 27.8 months and 11,811,849 yen for Cmab, and 22.6 months and 8,795,622 yen for Pmab. The incremental cost-effectiveness ratios to FOLFIRI were 736,743 yen/month for Bmab, 1,378,645 yen/month for Cmab, and 3,821,426 yen/month for Pmab. CONCLUSIONS: These findings suggested that these regimens were not sufficiently cost-effective, although they have excellent therapeutic efficacy. From the economic point of view, these combination regimens were inferior to FOLFIRI alone.

Cost-Effectiveness Analysis of First-Line FOLFIRI Combined With Cetuximab or Bevacizumab in Patients With RAS Wild-Type Left-Sided Metastatic Colorectal Cancer.

BACKGROUND: The FIRE-3 phase III clinical trial demonstrated the marked advantage of prolonging the median overall survival of patients with final RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC) by 38.3 months after treatment with irinotecan, fluorouracil, and leucovorin (FOLFIRI) plus cetuximab and by 28.0 months after treatment with FOLFIRI plus bevacizumab. However, the substantial cost increase and economic impact of using cetuximab imposes a considerable burden on patients and society. METHODS: A Markov model based on the data collected in the FIRE-3 trial was developed to investigate the cost-effectiveness of treating patients with FOLFIRI plus either cetuximab or bevacizumab from the perspective of the Chinese health-care system. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters. RESULTS: In our analysis, the total treatment costs in the bevacizumab and cetuximab groups were $92 549.31 and $94 987.31, respectively, and the QALYs gained were 1.58 and 2.05. In the base-case analysis, compared with bevacizumab, left-sided RAS WT patients receiving cetuximab gained 0.47 more QALYs at an ICER of $5187.23/QALY ($3166.23/LY). The 1-way sensitivity analysis showed that the most influential parameter was the cost of cetuximab. Probabilistic sensitivity analysis indicated that the cost-effective probability of cetuximab group was 92.8% under the willingness-to-pay threshold of $24 081. CONCLUSIONS: Treatment with FOLFIRI plus cetuximab in Chinese patients with left-sided RAS WT mCRC may improve health outcomes and use financial resources more efficiently than FOLFIRI plus bevacizumab.

Patient-based cost-effectiveness analysis of FOLFIRI versus FOLFOX7 for advanced gastric adenocarcinoma in China: A 4-year prospective randomised phase II study.

BACKGROUND: Using data from the 4-year follow-up results of an open, randomised, phase II study, this patient-based cost-effectiveness analysis compares mFOLFIRI (irinotecan, 5-fluorouracil and leucovorin, the IRI arm) with mFOLFOX7 (oxaliplatin, 5-fluorouracil and leucovorin, the OXA arm) as first-line treatments in patients with locally advanced gastric adenocarcinoma (GC). METHODS: A Markov model was created based on previous results reported at the 2016 Gastrointestinal Cancers Symposium to evaluate mFOLFIRI and mFOLFOX7 for advanced GC quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were examined as the primary outcomes. RESULTS: For the evaluable 128 patients, treatment efficacy was 0.59 QALYs for the IRI arm and 0.70 QALYs for the OXA arm, with a total cost of $13,861.34 for the IRI arm and $14,127.30 for the OXA arm. Hence, the ICER was $2,417.82 per QALY the OXA arm, which was below the threshold of 3 × per capita GDP of China. For subgroup analysis of those receiving mFOLFIRI followed by mFOLFOX7 (the IRI arm) and the reverse (the OXA arm), the OXA arm gained 0.44 more QALYs than the IRI arm with a total cost of $28,890.09 for the IRI arm and $31,147.30 for the OXA arm. However, the cost per QALY was also lower for the OXA arm than for the IRI arm, and the cost per QALY gained was $5,129.55 (below the Chinese WTP). CONCLUSION: mFOLFOX7 is a very high cost-effective alternative as the first-line treatment for those patients with advanced GC compared with mFOLFIRI.

Time-Series Modeling and Simulation for Comparative Cost-Effective Analysis in Cancer Chemotherapy: An Application to Platinum-Based Regimens for Advanced Non-small Cell Lung Cancer.

The purpose of this study was to propose a time-series modeling and simulation (M&S) strategy for probabilistic cost-effective analysis in cancer chemotherapy using a Monte-Carlo method based on data available from the literature. The simulation included the cost for chemotherapy, for pharmaceutical care for adverse events (AEs) and other medical costs. As an application example, we describe the analysis for the comparison of four regimens, cisplatin plus irinotecan, carboplatin plus paclitaxel, cisplatin plus gemcitabine (GP), and cisplatin plus vinorelbine, for advanced non-small cell lung cancer. The factors, drug efficacy explained by overall survival or time to treatment failure, frequency and severity of AEs, utility value of AEs to determine QOL, the drugs' and other medical costs in Japan, were included in the model. The simulation was performed and quality adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. An index, percentage of superiority (%SUP) which is the rate of the increased cost vs. QALY-gained plots within the area of positive QALY-gained and also below some threshold values of the ICER, was calculated as functions of threshold values of the ICER. An M&S process was developed, and for the simulation example, the GP regimen was the most cost-effective, in case of threshold values of the ICER=$70000/year, the %SUP for the GP are more than 50%. We developed an M&S process for probabilistic cost-effective analysis, this method would be useful for decision-making in choosing a cancer chemotherapy regimen in terms of pharmacoeconomic.

Real-world cost analysis of chemotherapy for colorectal cancer in Japan: detailed costs of various regimens during the entire course of chemotherapy.

BACKGROUND: Various chemotherapy regimens for advanced colorectal cancer have been introduced to clinical practice in Japan over the past decade. The cost profiles of these regimens, however, remain unclear in Japan. To explore the detailed costs of different regimens used to treat advanced colorectal cancer during the entire course of chemotherapy in patients treated in a practical setting, we conducted a so-called "real-world" cost analysis. METHOD: A detailed cost analysis was performed retrospectively. Patients with advanced colorectal cancer who had received chemotherapy in a practical healthcare setting from July 2004 through October 2010 were extracted from the ordering system database of Showa University Hospital. Direct medical costs of chemotherapy regimens were calculated from the hospital billing data of the patients. The analysis was conducted from a payer's perspective. RESULTS: A total of 30 patients with advanced colorectal cancer were identified. Twenty patients received up to second-line treatment, and 8 received up to third-line treatment. The regimens identified from among all courses of treatment in all patients were 13 oxaliplatin-based regimens, 31 irinotecan-based regimens, and 11 regimens including molecular targeted agents. The average (95% confidence interval [95% CI]) monthly cost during the overall period from the beginning of treatment to the end of treatment was 308,363 (258,792 to 357,933) Japanese yen (JPY). According to the type of regimen, the average monthly cost was 418,463 (357,413 to 479,513) JPY for oxaliplatin-based regimens, 215,499 (188,359 to 242,639) JPY for irinotecan-based regimens, and 705,460 (586,733 to 824,187) JPY for regimens including molecular targeted agents. Anticancer drug costs and hospital fees accounted for 50 to 77% and 11 to 25% of the overall costs of chemotherapy, respectively. CONCLUSION: The costs of irinotecan-based regimens were lower than those of oxaliplatin-based regimens and regimens including molecular targeted agents in Japan. Using a lower cost regimen for first-line treatment can potentially reduce the overall cost of chemotherapy. The main cost drivers were the anticancer drug costs and hospitalization costs.

Comparative cost-effectiveness of bevacizumab-irinotecan-fluorouracil versus irinotecan-fluorouracil in first-line metastatic colorectal cancer.

PURPOSE: To evaluate the cost-effectiveness of the addition of bevacizumab to the irinotecan-fluorouracil (Douillard regimen-CPT-FUFA-) in first-line treatment of metastatic colorectal cancer in a single-institution population. METHODS: Controlled, nonrandomized retrospective observational study. Treatment-naïve metastatic colorectal cancer patients received CPT-FUFA (January 2000-December 2003; control group) and bevacizumab_CPT-FUFA (January 2007-December 2010; study group). Variables related to: patient, clinical response (number of disease progression or death events, progression-free survival) and treatment (antineoplastic dose reduction, incremental cost/treated patient associated with the addition of bevacizumab). STATISTICAL ANALYSIS: median progression-free survival (Kaplan-Meier method), and hazard ratio (Cox regression). Survival curves were compared (Mantel-Haenszel test). RESULTS: In all, 69 patients were included: 32 (57.2 years -95%CI: 54.0-60.5-, 65.6% men) in CPT-FUFA group and 37 (68.1 years - 95%CI: 65.5-70.7-, 78.4% men) in bevacizumab_CPT-FUFA group. The disease progression or death events were 29 (90.6%) in CPT-FUFA group and 34 (91.9%) in bevacizumab_CPT-FUFA group. Median progression-free survival was 10.1 months (95%CI: 7.1-12.2) in CPT-FUFA and 11.0 months (95%CI: 7.6-12.6) in bevacizumab_CPT-FUFA (hazard ratio = 1.22; 95%CI: 0.7-2.1). Dose reductions: irinotecan and fluorouracil 11% (range: 4-20) in 5/32 (15.6%) CPT-FUFA patients and 25% (range: 8-35) in 18/37 (48.6%) bevacizumab_CPT-FUFA patients; Bevacizumab 30% (range: 4-50) in 20/37 (54.1%) bevacizumab_CPT-FUFA patients. The incremental cost associated with the addition of bevacizumab was 12,696.5 (IC95%:10,860.8-14,532.1) euros/patient. CONCLUSION: The addition of bevacizumab to the irinotecan-fluorouracil regimen, does not improve progression-free survival in our study population but increases costs per treated patient. These results potentially compromise the cost-effectiveness of the Bevacizumab_CPT-FUFA regimen.

Cost-effectiveness of Sacituzumab Govitecan versus Single-agent Chemotherapy for Patients with Metastatic Triple-Negative Breast Cancer in China.

INTRODUCTION: Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and survival outcomes. Sacituzumab govitecan was newly approved into Chinese market for mTNBC. However, whether its price matches the survival benefit still needs exploring. Here, this study aimed to evaluate the cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with mTNBC from the perspective of Chinese healthcare system. METHODS: A partitioned survival model consisting of three discrete health states was constructed to assess the cost-effectiveness of sacituzumab govitecan versus single-agent chemotherapy. The key clinical data in the model were from the ASCENT trial. Costs and utility inputs were collected from published literatures. Life-years gained, quality adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits, and incremental net monetary benefits were calculated between 2 treatment strategies. One-way and probabilistic sensitivity analyses were conducted to account for uncertainty and verify model robustness. Subgroup and cost-threshold analysis were also performed. RESULTS: Sacituzumab govitecan provided an additional 0.25 QALYs and an incremental cost of $ 81,778.61 compared with chemotherapy, which was associated with an ICER of $ 323,603.84/QALY. One-way sensitivity analysis revealed that the model was most sensitive to the cost of sacituzumab govitecan, weight, and utility of progression-free survival. The probabilistic sensitivity analysis indicated that the probability of sacituzumab govitecan being cost-effective was 0%. Considering a willingness-to-pay (WTP) of 3 times GDP, the maximum cost of sacituzumab govitecan that would make it cost-effective was $155.65 per unit (180 mg). CONCLUSIONS: Sacituzumab govitecan was not cost-effective for patients with mTNBC compared with chemotherapy at the commonly adopted WTP threshold of 3 times GDP per capita per QALY in China.

Budget impact analysis of introducing fruquintinib for metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and biologics in the United States from the payer perspective.

AIMS: Fruquintinib is a selective small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 recently approved in the United States (US) for the treatment of adult patients with metastatic colorectal cancer (CRC) who have previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, anti-epidermal growth factor receptor therapy. This study aimed to estimate the 5-year budget impact of fruquintinib from a US payer perspective (commercial and Medicare). MATERIALS AND METHODS: A budget impact model was developed to compare two scenarios: a reference scenario in which patients received regorafenib, trifluridine/tipiracil, or trifluridine/tipiracil with bevacizumab and an alternative scenario in which patients received reference scenario treatments or fruquintinib. Market shares were evenly divided across available options. A 5-year time horizon and a hypothetical health plan of 1 million members was assumed. The model included epidemiological inputs to estimate the eligible population; clinical inputs for treatment duration, progression-free survival, overall survival, and adverse event (AE) frequency; and cost inputs for treatment, AEs, disease management, subsequent therapy, and terminal care costs. Budget impact was reported as total, per member per year (PMPY), and per member per month (PMPM). RESULTS: The model estimated an eligible population of 194 patients (39 per year) over 5 years. In the base case, the estimated 5-year budget impact of fruquintinib was $4,077,073 ($0.82 PMPY and 0.07 PMPM) for a commercial health plan. During the first year, the estimated budget impact was $627,570 ($0.63 PMPY and 0.05 PMPM). Results were robust across sensitivity analyses. PMPM costs from the Medicare perspective were greater than the base-case (commercial) ($0.17 vs. $0.07) due to higher incidence of CRC in that population. CONCLUSIONS: Fruquintinib is associated with a low budget impact for payers based on proposed thresholds in the US.

Fruquintinib is a treatment for metastatic colorectal cancer that has progressed after or not responded to multiple guideline-recommended therapies. This budget impact analysis was conducted to estimate the added costs a health plan would incur over a 5-year period if it chose to cover this therapy. The analysis found that the per plan member per month cost of covering fruquintinib was $0.07 for a United States commercial health plan and $0.17 for Medicare.

Adverse event costs of systemic therapies for metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy and biologics in the US.

Aim: The objective of this study was to compare adverse event (AE) management costs for fruquintinib, regorafenib, trifluridine/tipiracil (T/T) and trifluridine/tipiracil+bevacizumab (T/T+bev) for patients with metastatic colorectal cancer (mCRC) previously treated with at least two prior lines of therapy from the US commercial and Medicare payer perspectives. Materials & methods: A cost-consequence model was developed to calculate the per-patient and per-patient-per-month (PPPM) AE costs using rates of grade 3/4 AEs with incidence ≥5% in clinical trials, event-specific management costs and duration treatment. Anchored comparisons of AE costs were calculated using a difference-in-differences approach with best supportive care (BSC) as a common reference. AE rates and treatment duration were obtained from clinical trials: FRESCO and FRESCO-2 (fruquintinib), RECOURSE (T/T), CORRECT (regorafenib) and SUNLIGHT (T/T, T/T+bev). AE management costs for the commercial and Medicare perspectives were obtained from publicly available sources. Results: From the commercial perspective, the AE costs (presented as per-patient, PPPM) were: $4015, $1091 for fruquintinib (FRESCO); $4253, $1390 for fruquintinib (FRESCO-2); $17,110, $11,104 for T/T (RECOURSE); $9851, $4691 for T/T (SUNLIGHT); $8199, $4823 for regorafenib; and $11,620, $2324 for T/T+bev. These results were consistent in anchored comparisons: the difference-in-difference for fruquintinib based on FRESCO was -$1929 versus regorafenib and -$11,427 versus T/T; for fruquintinib based on FRESCO-2 was -$2257 versus regorafenib and -$11,756 versus T/T. Across all analyses, results were consistent from the Medicare perspective. Conclusion: Fruquintinib was associated with lower AE management costs compared with regorafenib, T/T and T/T+bev for patients with previously treated mCRC. This evidence has direct implications for treatment, formulary and pathways decision-making in this patient population.

Cost comparison and economic implications of commonly used originator and generic chemotherapy drugs in India.

Cancer treatments have improved outcomes but access to medications is an issue around the world and especially so in low- and middle-income countries, such as India. Generic substitution may lead to significant cost savings. The author aimed to compare the cost and estimate potential cost savings per cycle, per patient, and for the country as a whole with generic substitution of frequently used chemotherapy drugs in the treatment of common cancers in India. Generic paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine, oxaliplatin and irinotecan cost from 8.9% to 36% of their equivalent branded originator drug, resulting in cost savings of ~ Indian Rupees (INR) 11,000 to >INR 90,000 (USD 200-1600, Euro 160-1300) per cycle; and ~INR 50,000 to >INR 240,000 (USD 900-4300, Euro 700-3400) per patient. Overall, potential yearly savings for health systems in India were nearly INR 47 billion (~USD 843 million, Euro 670 million). In conclusion, generic substitution for frequently used chemotherapy drugs in the treatment of common cancers has an enormous potential to generate significant cost savings and increase access to cancer treatments in India and other low- and middle-income countries.

Cost-effectiveness of cetuximab, cetuximab plus irinotecan, and panitumumab for third and further lines of treatment for KRAS wild-type patients with metastatic colorectal cancer.

OBJECTIVES: To estimate the cost-effectiveness of cetuximab monotherapy, cetuximab plus irinotecan, and panitumumab monotherapy compared with best supportive care (BSC) for the third and subsequent lines of treatment of patients with Kirsten rat sarcoma wild-type metastatic colorectal cancer from the perspective of the UK National Health Service. METHODS: An "an area under the curve" cost-effectiveness model was developed. The clinical effectiveness evidence for both cetuximab and panitumumab was taken from a single randomized controlled trial (RCT) in each case and for cetuximab plus irinotecan from several sources. RESULTS: Patients are predicted to survive for approximately 6 months on BSC, 8.5 months on panitumumab, 10 months on cetuximab, and 16.5 months on cetuximab plus irinotecan. Panitumumab is dominated, and cetuximab is extended dominated. An incremental cost-effectiveness ratio (ICER) of £95,000 per quality-adjusted life-year (QALY) was estimated for cetuximab versus BSC and is likely to be relatively accurate, because the relevant clinical evidence is taken from a high-quality RCT. The estimated ICER for panitumumab versus BSC, at £187,000 per QALY, is less certain due to assumptions in the adjustment for the substantial crossing-over of patients in the RCT. The ICER for cetuximab plus irinotecan versus BSC, at £88,000 per QALY, is least certain due to substantial uncertainty about progression-free survival, treatment duration, and overall survival. Nonetheless, when key parameters are varied within plausible ranges, all three treatments always remain poor value for money. CONCLUSIONS: All three treatments are highly unlikely to be considered cost-effective in this patient population in the United Kingdom. We explain how the reader can adapt the model for other countries.

Cost-effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany.

The objective of this study was to determine the cost-effectiveness of testing for KRAS mutations before administering EGFR inhibitors such as cetuximab and panitumumab for patients with advanced metastatic colorectal cancer (mCRC) in the United States and Germany. We developed a lifetime Markov model of costs and survival associated with treating mCRC patients to assess the impact of KRAS testing before administering EGFR inhibitor-containing chemotherapy regimens. Overall, combination therapies involving cetuximab plus irinotecan/FOLFIRI had a better life expectancy (25.83 weeks) than cetuximab or panitumumab alone. Use of KRAS testing (assuming KRAS mutant patients receive only irinotecan) was equally effective and saved $12,428 per patient in the United States. When KRAS mutant patients received best supportive care, the life expectancy decreased slightly (24.26 weeks vs. 25.83 weeks) and the costs decreased by $13,501 in the United States and €9,560 in Germany. For patients treated with cetuximab alone, use of KRAS testing to identify mutations lowered costs by $8,040 per patient in the U.S. analysis and €3,856 per patient in the German analysis. For patients treated with panitumumab alone, use of KRAS testing to identify mutations lowered costs by $7,546 per patient in the U.S. analysis and €4,612 per patient in the German analysis. Model results were sensitive to the cost of chemotherapy regimens and the prevalence of KRAS mutations in the population. Under most scenarios, using KRAS testing to select patients for EGFR inhibitor therapy saved $7,500-$12,400 per patient in the United States and €3,900-€9,600 per patient in Germany with equivalent clinical outcomes.

Comparative and cost-effectiveness of oxaliplatin-based or irinotecan-based regimens compared with 5-fluorouracil/leucovorin alone among US elderly stage IV colon cancer patients.

BACKGROUND: Clinical trials have shown a statistically significant disease-free survival benefit of oxaliplatin-based or irinotecan-based combination regimens for stage IV colon cancer. Less is known regarding the comparative effectiveness and cost-effectiveness of these agents among elderly patients. Whether the benefits of these agents justify the additional costs for elderly Medicare recipients is particularly policy relevant after US health care reform. METHODS: A cost-effectiveness analysis of oxaliplatin-based or irinotecan-based combination therapy versus 5-fluorouracil/leucovorin alone in elderly stage IV colon cancer patients was performed from a US Medicare perspective. Survival and direct medical costs were estimated using Surveillance, Epidemiology, and End Results-Medicare data sets for patients diagnosed from 2002 to 2005 with follow-up through 2007. Incremental cost-effectiveness ratios (ICERs) were calculated as costs per life-year gained, with sensitivity analysis estimating the cost per quality-adjusted life-year (QALY). RESULTS: Median improved overall survival with 5-fluorouracil/leucovorin alone, or irinotecan-based or oxaliplatin-based combination therapy was 0.99, 1.07, and 1.47 life-years, respectively. Costs per life-year gained for oxaliplatin-based or irinotecan-based combination regimens compared with 5-fluorouracil/leucovorin alone were $78,181 and $267,938, respectively. ICERs comparing oxaliplatin-based to irinotecan-based regimens were $40,230 per life-year gained or $160,920 per QALY. CONCLUSIONS: Oxaliplatin-based or irinotecan-based combination therapy improves overall survival but also substantially increases direct medical costs compared with 5-fluorouracil/leucovorin alone when used in elderly US patients with stage IV colon cancer. Oxaliplatin-based regimens are more cost-effective than irinotecan-based regimens for treatment of elderly stage IV colon cancer patients in terms of cost per life-year gained, but not in terms of cost per QALY.

The cost-effectiveness of different chemotherapy strategies for patients with poor prognosis advanced colorectal cancer (MRC FOCUS).

OBJECTIVES: To assess the value for money of alternative chemotherapy strategies for managing advanced colorectal cancer using irinotecan or oxaliplatin, either in sequence or in combination with fluorouracil. METHODS: A cost-effectiveness model was developed using data from the U.K. fluorouracil, oxaliplatin, and CPT11 (irinotecan)--use and sequencing (FOCUS) trial. The analysis adopted the perspective of the U.K. National Health Service. Input parameters were derived using a system of risk equations (for probabilities), count data regression models (for resource use), and generalized linear models (for utilities). Parameter estimates were obtained using Markov chain Monte Carlo methods, propagating the simulation values through the state-transition model to characterize appropriately the joint distributions of expected cost, survival and quality-adjusted life years for each treatment strategy. An acceptability frontier was used to represent the probability that the optimal option is cost-effective at different values of the cost-effectiveness threshold. RESULTS: The base-case analysis used drug unit costs provided by a typical English hospital. First-line doublet therapy combination therapy fluorouracil (5FU) plus irinotecan was the most cost-effective strategy at standard thresholds, with an incremental cost-effectiveness ratio (ICER) of £14,877 (pound sterling) compared with first-line 5FU until treatment failure followed by single agent irinotecan. Other strategies were all subject to extended dominance. A sensitivity analysis using published drug (list) prices found the most cost-effective strategy would be first-line fluorouracil until failure followed by 5FU plus irinotecan (ICER: £19,753). CONCLUSIONS: The combination of 5FU and irinotecan (whether used first or second line) appears to be more cost-effective than the single agent sequential therapies used in the FOCUS trial, or 5FU plus oxaliplatin.

Cost identification of Nordic FLIRI, Nordic FLOX, XELIRI and XELOX in first-line treatment of advanced colorectal cancer in Sweden -- a clinical practice model approach.

INTRODUCTION: The role of health-related economy is crucial due to the finite healthcare resources. Intravenous (i.v.) regimes Nordic FLOX and Nordic FLIRI, and the partly oral alternatives XELIRI and XELOX are four commonly used chemotherapies in the first-line treatment of advanced colorectal cancer (CRC) in the Scandinavian countries, all with different costs. AIM: To describe and compare costs associated with four commonly used treatments for advanced CRC in clinical routine practice. An additional aim was to evaluate the theoretical cost impact of adverse effects associated with the therapies. MATERIAL AND METHODS: The retrospective study was carried out using observations and a clinical quality database of CRC patients treated with Nordic FLOX, Nordic FLIRI, XELIRI and XELOX as first line at an oncology clinic in Gothenburg, Sweden. The treatments are used in parallel in clinical practice. All patients treated from 2003 to 2009 were included. The clinical outcome of the therapies was equivalent; mean treatment time was 5.9-7.7 months. A clinical economic evaluation model was designed. All direct costs associated with the baseline treatment, administration of chemotherapy and drug costs were collected and evaluated. RESULTS: The maximum cost for the four treatments was estimated to be 72 000-75 000 SEK per patient for six months, of this approximately 8000 SEK was linked to treatment of toxicity. During six months the i.v. treatments could include 17 more outpatient visits per patient compared to the oral alternatives. During treatment at the clinic around 20% of the patients were hospitalised (XELOX excluded, because of few included patients). CONCLUSION: The results indicate that the four regimens are similar in terms of treatment costs. Different costs affect the total cost. The oral alternative makes it possible to treat additional patients with the same labour force resources. Treatment of adverse effects contributes to extensive resource use at the hospital.

The evolving role of monoclonal antibodies in colorectal cancer: early presumptions and impact on clinical trial development.

Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plateau of FDA-approved agents for the treatment of mCRC, pivotal results have developed that critically affect the care for these patients. Correlative data from randomized trials of EGFR inhibitors across disease settings have demonstrated higher response rates, specifically for patients with wild-type K-RAS tumors. The interpretation of the B-RAF mutation and other molecular markers may further define the appropriateness of anti-EGFR therapy. Recent literature revealed that the first-line use of combined anti-EGFR therapy plus bevacizumab resulted in inferior outcomes and additional toxicities. Furthermore, the role of biologic agents for locally advanced colon cancer cannot be advocated at this time. With impending changes in the health care system, the economic impact of mAbs will continue to be scrutinized. Hence, as the significance of molecular markers continues to develop, their role as it pertains to the appropriate use of biologic agents in the treatment of mCRC will continue to evolve.

Clinical and economic evaluation of first-line therapy with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer.

OBJECTIVE: Recently, significant progress in treatment of metastatic colorectal cancer has been achieved. Either FOLFIRI (fluorouracil, leucovorin and irinotecan) or modified FOLFOX6 (fluorouracil, leucovorin and oxaliplatin, oxaliplatin dose 85 mg/m(2)) is selected as first-line therapy in clinical practice in Japan. However, economic burden of colorectal cancer is considerable. METHODS: Analysis was made for all patients who were treated with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer. Regimen of FOLFIRI was compared with modified FOLFOX6 under consideration from clinical and economic standpoints. Progression free survival, response, toxicity and cancer care cost in patients with metastatic colorectal cancer was analyzed. Direct costs based on the fee schedule of the Japanese national health insurance were calculated. RESULTS: Median progression free survival was 7.7 months for FOLFIRI versus 8.4 months for modified FOLFOX6 (P = 0.48). Overall cost for first four cycles was yen756 284 for FOLFIRI and yen1 081 162 for modified FOLFOX6 (P < 0.0001). All grade alopecia was significantly more frequent with FOLFIRI than with modified FOLFOX6 (P = 0.04). All grade neuropathy was more observed with modified FOLFOX6 than FOLFIRI (P = 0.0002). CONCLUSIONS: FOLFIRI is inexpensive in the initial stage of treatment which a number of patients can receive chemotherapy than modified FOLFOX6 as first-line therapy for metastatic colorectal cancer in Japanese national insurance system.

Pharmacoeconomic aspects of FOLFIRI or FOLFOX regimens administered with a fully ambulatory pump compared to the day hospital setting.

AIMS AND BACKGROUND: The social cost of management of patients suffering from colorectal cancer has been growing dramatically in the last decade due to the high number of active antitumor agents and to the increased incidence of the tumor in western countries. The aim of the study was to explore from a pharmacoeconomic point of view a different way to administer the two most common regimens in this patient setting. STUDY DESIGN: This was a cost-minimization study. Data were extracted from hospital registries and dedicated offices. The traditional setting (day hospital inpatient setting) and a fully ambulatory setting (CIP pump) were considered and compared. RESULTS: The CIP system resulted in higher direct costs than the day hospital setting (444.70 versus 159.00 euro/cycle). However, traditional infusion resulted in longer nursing care, with an increase in nursing costs of more than 100.00 euro/cycle. Moreover, the inpatient setting obliged patients to stay in the hospital as much as ten times longer than with the CIP system. This meant that with the same time span and the same resources, the CIP pump permitted treatment of at least five times more patients than the traditional setting. Thus, a threshold of 52.00 euro per patient for general hospital costs (ordinary and extraordinary maintenance of buildings, power supply, and housekeeping) was identified to discriminate whether the CIP pump is cost-saving or not. CONCLUSIONS: Administration of the FOLFIRI or FOLFOX regimen in a traditional day hospital setting was less costly when considering the direct costs. However, a fully ambulatory pump permitted to better employ hospital resources and could permit cost-saving in those units in which more than five patients per day are treated and global costs are higher than 52.00 euro per patient.

Cost-effectiveness of Capecitabine + Irinotecan Versus Leucovorin + Fluorouracil + Irinotecan in the Second-line Treatment of Metastatic Colorectal Cancer in China.

PURPOSE: The AXEPT trial demonstrated that modified XELIRI (mXELIRI; capecitabine + irinotecan) was noninferior to standard treatment with FOLFIRI (fluorouracil + leucovorin + irinotecan), both ± bevacizumab, in the treatment of metastatic colorectal cancer (mCRC). The present study was designed to evaluate the cost-effectiveness of mXELIRI versus FOLFIRI as a second-line treatment of mCRC. METHODS: We developed a Markov model to estimate the costs and health outcomes of mXELIRI and FOLFIRI in patients with mCRC from the Chinese payer perspective. Survival data, transition probabilities, and health utility values were obtained from published studies. The costs of drugs were obtained from the West China Hospital. Life-years (LYs), quality-adjusted life-years (QALYs) gained, incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER) values were regarded as the primary end points. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the impact of uncertainty of parameters in the analysis. FINDINGS: The effectiveness was found to be 0.48 QALYs (1.14 LYs) in the mXELIRI arm and 0.41 QALYs (1.05 LYs) in the FOLFIRI arm, with total costs of 29,896.41 US dollars (USD) in the mXELIRI arm and 28,894.68 USD in the FOLFIRI arm. The ICER and ICUR with mXELIRI versus FOLFIRI were 11,130.33 USD/LY and 14,310.43 USD/QALY gained, which were less than the willingness-to-pay threshold in China (25,840.88 USD/QALY). IMPLICATIONS: Based on the results of this study, mXELIRI was found to be a cost-effective alternative to FOLFIRI as a second-line treatment of mCRC in patients in China.