Cost-Effectiveness Analysis of Hepatic Arterial Chemotherapy for Advanced Hepatocellular Carcinoma in China: A Comparative Analysis of HAIC-FO and Sorafenib.

BACKGROUND The FOHAIC-1 trial showed hepatic arterial infusion chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) improved survival, compared with sorafenib, in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to conduct a cost-effectiveness comparison between HAIC-FO and sorafenib from the perspective of the Chinese healthcare system. MATERIAL AND METHODS The economic evaluation was conducted between July 2023 and February 2024, spanning a 10-year investment horizon. A Markov model was developed to perform a cost-effectiveness analysis of HAIC-FO vs sorafenib. Health states incorporated in the model comprised progression-free disease, progressed disease, and death. Transition probabilities were derived from data obtained from the FOHAIC-1 trial. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Additionally, one-way and probabilistic sensitivity analyses assessed the model's robustness. RESULTS The HAIC-FO group accrued a total cost of $22,781, whereas the sorafenib group totaled $18,795. In terms of effectiveness, the HAIC-FO group achieved 1.06 quality-adjusted life years (QALYs), whereas the sorafenib group attained 0.65 QALYs. Compared with sorafenib, HAIC-FO yielded an additional 0.41 QALYs at a cost of additional $3,985, resulting in an incremental cost of $9,720 per QALY gained. The one-way sensitivity analysis revealed the final ICER remained below the willingness-to-pay (WTP) threshold of $30,492 per QALY, when considering parameter fluctuations. Additionally, probabilistic sensitivity analysis indicated a 99.8% probability that the ICER for HAIC-FO compared with sorafenib would fall below the WTP threshold. CONCLUSIONS Compared with sorafenib, HAIC-FO emerged as a cost-effective first-line treatment option for patients facing advanced HCC in China.

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 of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

CDX2 Biomarker Testing and Adjuvant Therapy for Stage II Colon Cancer: An Exploratory Cost-Effectiveness Analysis.

OBJECTIVES: Adjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0) colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might benefit from adjuvant chemotherapy. We evaluated the cost-effectiveness of testing for the absence of CDX2 expression followed by adjuvant chemotherapy (fluorouracil combined with oxaliplatin [FOLFOX]) for patients with stage II colon cancer. METHODS: We developed a decision model to simulate a hypothetical cohort of 65-year-old patients with average-risk stage II colon cancer with 7.2% of these patients being CDX2-negative under 2 different interventions: (1) test for the absence of CDX2 expression followed by adjuvant chemotherapy for CDX2-negative patients and (2) no CDX2 testing and no adjuvant chemotherapy for any patient. We derived disease progression parameters, adjuvant chemotherapy effectiveness and utilities from published analyses, and cancer care costs from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Sensitivity analyses were conducted. RESULTS: Testing for CDX2 followed by FOLFOX for CDX2-negative patients had an incremental cost-effectiveness ratio of $5500/quality-adjusted life-years (QALYs) compared with no CDX2 testing and no FOLFOX (6.874 vs 6.838 discounted QALYs and $89 991 vs $89 797 discounted US dollar lifetime costs). In sensitivity analyses, considering a cost-effectiveness threshold of $100 000/QALY, testing for CDX2 followed by FOLFOX on CDX2-negative patients remains cost-effective for hazard ratios of <0.975 of the effectiveness of FOLFOX in CDX2-negative patients in reducing the rate of developing a metastatic recurrence. CONCLUSIONS: Testing tumors of patients with stage II colon cancer for CDX2 and administration of adjuvant treatment to the subgroup found CDX2-negative is a cost-effective and high-value management strategy across a broad range of plausible assumptions.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials. Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit. Design, Setting, and Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021. Exposures: First-line chemotherapy for advanced pancreatic cancer. Main Outcomes and Measures: The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching. Results: From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 [95% CI, 0.78-0.94]). Conclusions and Relevance: This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.

Cost-effectiveness analysis of FOLFIRINOX vs gemcitabine with nab-paclitaxel as adjuvant treatment for resected pancreatic cancer in the United States based on PRODIGE-24 and APACT trials.

BACKGROUND: Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. OBJECTIVE: To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. METHODS: A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). RESULTS: Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. CONCLUSIONS: Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. DISCLOSURES: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.

Conversion to biosimilar pegfilgrastim-cbqv enables budget-neutral access to FOLFIRINOX treatment for metastatic pancreatic cancer.

Aim: To estimate the cost-savings from conversion to biosimilar pegfilgrastim-cbqv that can be reallocated to provide budget-neutral expanded access to FOLFIRINOX in patients with metastatic pancreatic cancer. Methods: Simulation modeling in a panel of 2500 FOLFIRINOX-treated patients, using varying treatment duration (1-12 cycles) and conversion rates (10-100%), to estimate cost-savings and additional FOLFIRINOX treatment that could be budget neutral. Results: In a 2500-patient panel at 100% conversion, savings of US$6,907.41 per converted patient over 12 cycles of prophylaxis translate to US$17.3 million and could provide 72,273 additional FOLFIRINOX doses or 6023 full 6-month regimens. Conclusion: Conversion to biosimilar CIN/FN prophylaxis can generate significant cost-savings and provide budget-neutral expanded access to FOLFIRINOX treatment for patients with metastatic pancreatic cancer.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. The authors calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 2500 patients with metastatic pancreatic cancer and then computed the number of additional doses of FOLFIRINOX chemotherapy that could be purchased with those savings. Using biosimilar pegfilgrastim for 12 cycles could save US$6,907.41 per patient. If all 2500 patients were treated with biosimilar pegfilgrastim, US$17.3 million could be saved. This could provide 72,273 additional FOLFIRINOX doses. Biosimilar pegfilgrastim can generate significant savings to purchase chemotherapy for additional patients cost-free.

The economic burden of metastatic pancreatic cancer.

BACKGROUND: Objectives: Pancreatic cancer (PC) is a costly disease with a limited life-expectancy as it generally presents as an advanced, metastatic disease. Though current literature suggests cost varies by first line treatment, there is limited real-world knowledge about the economic burden of pancreatic cancer. This study describes the economic burden of pancreatic cancer patients overall and by observed first line treatments. METHODS: The IBM MarketScan databases were used to identify adult metastatic PC patients from January 1, 2010 through 3/31/2017. Those without other primary cancers, pregnancy, or prior PC treatment, and with 6 months of continuous enrollment prior to PC were included. Treatment patterns and healthcare utilization and expenditures were measured during the variable-length follow-up period. Continuous measures were presented as per patient per month (PPPM). RESULTS: A total of 6,360 patients met all inclusion criteria. Almost half (46.8%) of patients were untreated. Gemcitabine alone (15.6%) and FOLFIRINOX (11.4%) were the most commonly observed first line regimens. Treated patients incurred $17,513 PPPM (Gemcitabine alone) to $27,889 PPPM (FOLFIRINOX) during follow-up. Untreated patients incurred the highest unadjusted ($30,777 PPPM) and adjusted ($20,392 PPPM) cost. CONCLUSIONS: Metastatic PC patients incur a high economic burden driven by high utilization of healthcare resources, which varies by first line treatment. Also, the high proportion of untreated patients is alarming as these patients may be the most expensive of all patients. There is an unmet need in these patients for effective treatments that also reduce their economic burden.

Comparative Cost-effectiveness of Aflibercept and Ramucirumab in Combination with Irinotecan and Fluorouracil-based Therapy for the Second-line Treatment of Metastatic Colorectal Cancer in Japan.

PURPOSE: The addition of aflibercept (AFL) or ramucirumab (RAM) to folinic acid, fluorouracil, and irinotecan (FOLFIRI) prolongs overall survival and progression-free survival compared with FOLFIRI alone in patients with metastatic colorectal cancer (mCRC) as second-line therapy. Although these combination regimens are recommended among the standard therapies, significant additional cost is a concern. The comparative cost-effectiveness of AFL and RAM was examined from the perspective of the Japanese health care payer. METHODS: A partitioned survival analysis was constructed. The data sources were the VELOUR (Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen) and RAISE (Ramucirumab Versus Placebo in Combination With Second-Line FOLFIRI in Patients With Metastatic Colorectal Carcinoma That Progressed During or After First-Line Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine) trials, which compared FOLFIRI alone with AFL or RAM in second-line treatment for mCRC. The cost and effectiveness of the combination of AFL or RAM with FOLFIRI were compared with those of FOLFIRI alone and examined between both agents in a 10-year time horizon. The health outcomes were life-years (LYs) and quality-adjusted life-years (QALYs). The costs were 2019 revisions to the drug prices and medical fees. The robustness of the model was verified by 1-way sensitivity analyses and a probability sensitivity analysis. A 2% annual discount was applied to the expenses and QALYs. A willingness-to-pay threshold of ¥7.5 million was used. FINDINGS: Compared with FOLFIRI alone, combination AFL or RAM with FOLFIRI had incremental effects of 0.173 QALYs (0.253 LYs) and 0.137 QALYs (0.197 LYs), incremental costs of ¥3,423,481 (US $31,010) and ¥5,766,106 (US $52,229), and incremental cost-effectiveness ratios of ¥19, 836, 504 (US $179,678) and ¥41, 947, 989 (US $379,964) per QALY, respectively. Results of 1-way sensitivity analyses and probability sensitivity analysis all exceeded a willingness-to-pay threshold of ¥7.5 million. In the comparison of the 2 agents, AFL was a dominant over RAM. IMPLICATIONS: Adding AFL or RAM to FOLFIRI in the second line of mCRC treatment was not cost-effective in the Japanese health care system. On the basis of the results of this study, in the treatment of mCRC, it will be necessary to adjust the prices of AFL and RAM with the improvement of clinical parameters, such as survival time and adverse events. Of the 2 agents, AFL was more cost-effective than RAM.

Real-World Assessment of Health Care Costs for Patients with Metastatic Pancreatic Cancer Following Initiation of First-Line Chemotherapy.

BACKGROUND: Management of metastatic pancreatic ductal adenocarcinoma (mPDA) places a significant financial burden on the U.S. health care system because of such factors as treatment with multidrug chemotherapy regimens, management of chemotherapy-related adverse events, and disease- or treatment-related hospitalizations. Depending on functional status, first-line chemotherapy regimens that are guideline recommended include nab-paclitaxel with gemcitabine (AG) and FOLFIRINOX (FFX), the combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin. However, few previous studies have examined overall health care costs associated with mPDA management. OBJECTIVE: To describe health care costs following initiation of first-line treatment with AG or FFX among patients with mPDA. METHODS: Retrospective cohorts of first-line AG and FFX initiators were constructed from the MarketScan database (2014-2017). The index date was the date of first-line AG or FFX initiation. Included patients had insurance enrollment for 6 months before the index date. Total cumulative health care costs and costs from outpatient services, inpatient admissions, emergency department visits, chemotherapy administrations, and pharmacy dispensing were assessed within 12 months after the index date (i.e., 0-1, 0-2, …, 0-12 months). Patient-level cost data began accruing from the first paid claim and continued accruing until the censoring date. RESULTS: A total of 2,199 patients with mPDA initiated first-line AG (n = 1,352) or FFX (n = 847). Compared with AG initiators, FFX patients were younger (mean age 59 vs. 63 years) and had better baseline health status, with fewer having diabetes (43% vs. 57%) or coronary artery disease (12% vs. 22%). Median follow-up was 5.4 and 7.2 months for AG and FFX, respectively. Median first-line treatment duration was 2.1 months with AG and 2.3 months with FFX. Six months following first-line treatment initiation, total cumulative health care costs (median) were $85,714 (95% CI = $79,683-$91,788) and $114,116 (95% CI = $105,816-$119,591) for AG and FFX initiators, respectively. Outpatient services contributed the largest fractional cost for both groups. CONCLUSIONS: Total health care costs for patients with mPDA who initiated FFX or AG are driven mostly by outpatient rather than inpatient costs. Further research, using comparative methodology, is warranted to fully understand cost drivers and whether higher costs for FFX patients relate primarily to use of FFX or higher underlying use of outpatient care among FFX patients. DISCLOSURES: This study was funded by Halozyme Therapeutics. Oestreicher and Yeganegi were employees of Halozyme Therapeutics at the time of the study and were involved in study design, data interpretation, and the decision to submit the data for publication. Bullock reports advisory board fees from Eisai, Exelixis, Bayer, and Taiho and consulting fees from Halozyme Therapeutics, outside the submitted work. Rowan reports consulting fees from Halozyme Therapeutics, during the conduct of the study. Chiorean reports grants and consulting fees from Celgene and Halozyme Therapeutics; grants from Lilly, Stemline, Ignyta, Roche, Merck, Boehringer-Ingelheim, Bristol Meyer Squibb, Incyte, Macrogenics, Rafael, and AADi; and consulting fees from Astra Zeneca, Array, Eisai, Ipsen, Five Prime Therapeutics, Seattle Genetics, Vicus, and Legend, outside the submitted work.

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.

Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial.

OBJECTIVES: Cetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX-4) is superior to FOLFOX-4 alone as a first-line treatment for patients with metastatic colorectal cancer with RAS wild-type (RAS wt mCRC), with significantly improved survival benefit by TAILOR, an open-label, randomised, multicentre, phase III trial. Nevertheless, the cost-effectiveness of these two regimens remains uncertain. The following study aims to determine whether cetuximab combined with FOLFOX-4 is a cost-effective regimen for patients with specific RAS wt mCRC in China. DESIGN: A cost-effectiveness model combined decision tree and Markov model was built to simulate pateints with RAS wt mCRC based on health states of dead, progressive and stable. The health outcomes from the TAILOR trial and utilities from published data were used respectively. Costs were calculated with reference to the Chinese societal perspective. The robustness of the results was evaluated by univariate and probabilistic sensitivity analyses. PARTICIPANTS: The included patients were newly diagnosed Chinese patients with fully RAS wt mCRC. INTERVENTIONS: First-line treatment with either cetuximab plus FOLFOX-4 or FOLFOX-4. MAIN OUTCOME MEASURES: The primary outcomes are costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Baseline analysis disclosed that the QALYs was increased by 0.383 caused by additional cetuximab, while an increase of US$62 947 was observed in relation to FOLFOX-4 chemotherapy. The ICER was US$164 044 per QALY, which exceeded the willingness-to-pay threshold of US$28 106 per QALY. CONCLUSIONS: Despite the survival benefit, cetuximab combined with FOLFOX-4 is not a cost-effective treatment for the first-line regime of patients with RAS wt mCRC in China. TRIAL REGISTRATION NUMBER: TAILOR trial (NCT01228734); Post-results.

Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line treatment of RAS wild-type metastatic colorectal cancer in Germany: data from the FIRE-3 (AIO KRK-0306) study.

Aims: This analysis evaluates the cost-effectiveness of first-line treatment with FOLFIRI + cetuximab vs FOLFIRI + bevacizumab for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in Germany based on the randomized phase 3 FIRE-3 trial. For patients with RAS wt mCRC, FOLFIRI + cetuximab yielded statistically significant median overall survival gains over FOLFIRI + bevacizumab.Materials and methods: A standard 3-state partitioned survival cost-utility model was developed to compare the health benefits and costs of treatment from a German social health insurance perspective using individual patient-level trial data. Health outcomes were reported in life-years (LYs) and quality-adjusted life-years (QALYs) gained. Survival was estimated based on Kaplan-Meier (KM) curves supplemented with best-fitting parametric survival model extrapolations. Subgroup analyses of patients with a left-sided primary tumor location or patients with metastases confined to the liver were performed.Results: In the modified intention-to-treat analysis, FOLFIRI + cetuximab, providing 0.68 additional LYs (0.53 QALYs), yielded incremental cost-effectiveness ratios (ICERs) of €36,360/LY and €47,250/QALY. In subgroup analyses, patients experienced improved survival gains without a corresponding increase in costs, resulting in lower ICERs. Our model was most sensitive to changes in treatment duration across all lines of therapy, utility of progressive disease, as well as patients' weight and body surface area.Limitations: This cost-effectiveness analysis was based on patient-level data from the FIRE-3 trial. Trial outcomes may not adequately reflect those in the real-world setting. Additionally, resource use and costs were obtained from tariff lists, which do not account for differences in treatment practice. These considerations limit generalizability of outcomes to other countries, or within the German healthcare setting.Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients with RAS wt mCRC, with ICERs well below willingness-to-pay thresholds for diseases with a high burden.

Model-Based Cost-Effectiveness Analysis of Panitumumab Plus FOLFIRI for the Second-Line Treatment of Patients with Wild-Type Ras Metastatic Colorectal Cancer.

INTRODUCTION: The NCT00339183 trial demonstrated that adding panitumumab to fluorouracil, leucovorin and irinotecan (FOLFIRI) as a second-line therapy of wild-type RAS metastatic colorectal cancer (mCRC) increases the median progression-free survival (PFS). Nevertheless, panitumumab is not yet approved in China, and the costs and outcomes of the therapy are still unclear. We estimated the cost-effectiveness of this intervention from the perspective of Chinese health care systems by constructing two pricing scenarios for panitumumab. Scenario 1: Pricing is based on the price of a similar product (cetuximab) in China. Scenario 2: We estimated the value-based price. METHODS: A partitioned survival model was created based on the results of the NCT00339183 trial, which evaluated panitumumab plus FOLFIRI versus FOLFIRI. The model simulated the disease progression. We calculated medical costs from the perspectives of the Chinese health care systems. The primary outcome measures were costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: In scenario 1, compared with FOLFIRI alone, FOLFIRI with panitumumab arm had an ICER of ¥1,539,988/QALY. The most influential factors were the mean overall survival (OS), utility before progression and cost of panitumumab. The probability of panitumumab plus FOLFIRI being cost-effective in China was 0% when the willingness-to-pay (WTP) threshold was ¥193,932/QALY. In scenario 2, when the cost of panitumumab was assumed to be ¥4032.61 or ¥5218.96 per cycle, the ICERs approximated the WTP thresholds of ¥193,932/QALY or ¥420,633/QALY, respectively. In this value-based pricing scenario, panitumumab plus FOLFIRI is estimated to be cost-effective. CONCLUSION: We construct two pricing scenarios in China. In scenario 1, panitumumab plus FOLFIRI as a second-line therapy of mCRC provided an incremental benefit, but simultaneously increased costs (at the current price) even further. In scenario 2, when the value-based price was adopted, panitumumab plus FOLFIRI was estimated to be cost-effective. Our study establishes a pricing framework for new anticancer drugs to reflect the economics of drugs. TRIAL REGISTRATION NUMBER: NCT00339183.

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.

Cost-effectiveness analysis of selective first-line use of biologics for unresectable RAS wild-type left-sided metastatic colorectal cancer.

Background: Evidence from a retrospective analysis of multiple large phase iii trials suggested that primary tumour location (ptl) in RAS wild-type metastatic colorectal cancer (wtRAS mcrc) might have predictive value with respect to response to drug therapies. Recent studies also show a potential preferential benefit for epidermal growth factor inhibitors (egfris) for left-sided tumours. In the present study, we aimed to determine the incremental cost-effectiveness ratio (icer) for the first-line use of an egfri for patients with left-sided wtRAS mcrc. Methods: We developed a state-transition model to determine the cost effectiveness of alternative treatment strategies in patients with left-sided mcrc:■ Standard of care■ Use of an egfri in first-line therapyThe cohort for the study consisted of patients diagnosed with unresectable wtRAS mcrc with an indication for chemotherapy and previously documented ptl. Model parameters were obtained from the published literature and calibration. The perspective was that of a provincial ministry of health in Canada. We used a 5-year time horizon and an annual discount rate of 1.5%. Results: Selecting patients for first-line egfri treatment based on left-sided location of their colorectal primary tumour was more effective than the standard of care, resulting in an increase in quality-adjusted life-years (qalys) of 0.226 (or 0.644 life-years gained). However, the strategy was also more expensive, costing an average of $60,639 more per patient treated. The resulting icer was $268,094 per qaly. A 35% price reduction in the cost of egfri would be needed to make this strategy cost-effective at a willingness-to-pay threshold (wtp) of $100,000 per qaly. Conclusions: Selective use of an egfri based on ptl was more cost-effective than unselected use of those agents; however, based on traditional wtp thresholds, it was still not cost-effective. While awaiting the elucidation of more precise predictive biomarkers that might improve cost-effectiveness, the price of egfris could be reduced to meet the wtp threshold.

FOLFIRINOX is a cost-effective combination chemotherapy in first-line for advanced pancreatic Cancer.

OBJECTIVES: The analysis was conducted to assess the effect of front-line combination chemotherapies on progression free survival (PFS). METHODS: The analysis was restricted to phase III randomized controlled trials (RCTs) in first-line therapy for advanced pancreatic cancer. The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) was applied to the above phase III RCTs. We have also calculated differences in PFS between the different arms of each trial and the pharmacological costs necessary to get the benefit in PFS, for each trial. RESULTS: Our study evaluated 11 phase III randomized controlled trials (RCTs), including 4572 patients. Combining the costs of therapy with the measure of efficacy represented by the PFS, we have obtained 74.12 € per month of PFS gained for 5-FU, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX), 90.14 per month of PFS gained for gemcitabine and oxaliplatin (GEMOX) and 4708.70 € per month of PFS gained for the combination of gemcitabine plus nab-pacliatxel against gemcitabine alone. CONCLUSIONS: Combining pharmacological costs with the measure of efficacy represented by PFS, FOLFIRINOX is a cost-effective first-line for advanced pancreatic cancer.

Quality of life and cost of strategies of two chemotherapy lines in metastatic colorectal cancer: results of the FFCD 2000-05 trial.

Objectives: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). Methods: Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation. Valuations were made using 2009 and 2016 tariffs. QoL was assessed using the QLQ-C30 questionnaire and clinically significant variations were searched. Results: In 2009, the mean cost per patient was significantly lower for the sequential strategy compared to the combination strategy (18,061€ and 23,119€, p = 0.001). In 2016, the difference was no longer significant (16,876€ and 18,090€, p = 0.41) because oxaliplatin and irinotecan became generics. The QoL analysis (292 patients) showed that there was significantly less improvement of global health status in the sequential strategy than in the combination strategy (29% and 42%; p = 0.02) during first-line therapy. No significant differences were observed for emotional functioning (p = 0.45) and physical functioning (p = 0.07) or during second-line therapy. Conclusion: The choice to treat patients with advanced colorectal cancer using one or the other strategy cannot be based on costs or QoL.

Managing the economic impact of advanced pancreatic cancer.

Pancreatic cancer is typically diagnosed in the late stage of the disease, making it the fourth leading cause of cancer-related death in the United States. It is also one of the few cancers with an increasing incidence, particularly in the younger population. By 2030, it is expected to become the second leading cause of cancer-related death. Patients with pancreatic cancer encounter monthly medical costs 15 times higher than those without, with costs highest in the later stages of the disease. Treatments for pancreatic cancer include surgery (available to fewer than 20% of newly diagnosed patients) and, for advanced disease, chemotherapy with gemcitabine with nab-paclitaxel or FOLFIRINOX, which can increase overall survival (OS) by a few months. Economic and outcome analyses of clinical data find no significant difference in OS between the 2 regimens, although FOLFIRINOX carries a much higher rate of serious adverse effects, limiting its use to patients with good performance status. In 2017, the FDA approved immunotherapy for patients with microsatellite instability-high or mismatch repair-deficient solid tumors, which occurs in approximately 1% of pancreatic cancer diagnoses. Several immunotherapies and targeted therapies are currently in clinical trials and may significantly alter the trajectory of the disease. However, they typically cost more than $100,000 per year, putting significant strain on payers. Thus, it is important that payers plan now for the potential arsenal of new treatments and identify opportunities to manage their utilization as well as patients with the disease to contain costs.

Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer.

BACKGROUND: Patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI-H/dMMR mCRC treatment. METHODS: The treatment of hypothetical patients with MSI-H/dMMR mCRC was simulated in 2 treatment scenarios: a third-line treatment and an exploratory first-line treatment. The treatments compared were nivolumab, ipilimumab and nivolumab, trifluridine and tipiracil (third-line treatment), and mFOLFOX6 and cetuximab (first-line treatment). Disease progression, drug toxicity, and survival rates were based on the CheckMate 142, study of TAS-102 in patients with metastatic colorectal cancer refractory to standard chemotherapies (RECOURSE), and Cancer and Leukemia Group B/Southwest Oncology Group 80405 trials. The analyzed outcomes included survival (life-years), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Ipilimumab with nivolumab was the most effective strategy (10.69 life-years and 9.25 QALYs for the third line; 10.69 life-years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life-years and 6.76 QALYs for the third line; 8.21 life-years and 7.00 QALYs for the first line), trifluridine and tipiracil (0.74 life-years and 0.07 QALYs), and mFOLFOX6 and cetuximab (2.72 life-years and 1.63 QALYs). However, neither checkpoint inhibitor therapy was cost-effective in comparison with trifluridine and tipiracil (nivolumab ICER, $153,000; ipilimumab and nivolumab ICER, $162,700) or mFOLFOX6 and cetuximab (nivolumab ICER, $150,700; ipilimumab and nivolumab ICER, $158,700). CONCLUSIONS: This modeling analysis found that both single and dual checkpoint blockade could be significantly more effective for MSI-H/dMMR mCRC than chemotherapy, but they were not cost-effective, largely because of drug costs. Decreases in drug pricing and/or the duration of maintenance nivolumab could make ipilimumab and nivolumab cost-effective. Prospective clinical trials should be performed to explore the optimal duration of maintenance nivolumab.