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.

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.

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 minimization comparison of oral UFT/leucovorin versus 5-fluorouracil/leucovorin as adjuvant therapy for colorectal cancer in Taiwan.

AIM: Oral uracil-tegafur/leucovorin (UFT/LV) and intravenous 5-fluorouracil (FU)/LV are common adjuvant therapies for Stages II and III colorectal cancer. This study aims to determine the most cost-effective treatment alternative between UFT/LV and 5-FU/LV in Stages II and III colorectal cancer from Taiwan's National Health Insurance perspective. PATIENTS & METHODS: The costs were referenced directly from the National Health Insurance reimbursement price. Chemotherapy regimen considered for the cost analysis calculation was adapted from NSABP-C-06 study, and, a time saving calculation was also included. In addition, we compare the treatment outcome. RESULT: A total cost saving of US$3620.80-$3709.16 per patient per treatment was achieved with the UFT/LV treatment. UFT/LV provides the comparable outcome to 5-FU/LV. CONCLUSION: UFT/LV was the more cost-effective treatment as adjuvant chemotherapy.

Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases.

BACKGROUND: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. METHODS: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. RESULTS: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. CONCLUSION: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

Effects of nutritional support on short-term clinical outcomes and immune response in unresectable locally advanced oesophageal squamous cell carcinoma.

This retrospective study investigated the efficiency of nutritional support in unresectable locally advanced oesophageal squamous cell carcinoma (LAOSCC) patients who received concurrent chemoradiotherapy (CCRT) based on 5-fluorouracil and cisplatin. In the routine care group, 63 patients served as historical controls and received nutrition support in a reactive manner. In addition, 57 patients in the nutritional support group received timely diet counselling, oral nutritional supplements, enteral nutrition and/or parenteral nutrition during CCRT. This support was based on scores from nutritional risk screening 2002 (NRS-2002) after June 2014. The nutritional support group had significant advantages over the routine care group with respect to the incidence of neutropenia, the objective response rate, the change in serum albumin and the lengths of hospital stay. In addition, the nutritional support group had significantly higher levels of IgG and IL-2, higher proportions of NK, CD3+ and CD4+ cells as well as a higher ratio of CD4+ /CD8+ cells than the routine care group (p < .05). In contrast, the nutritional support group had a significantly lower level of IL-6. In conclusion, the current nutritional care programme could bring benefits of improving treatment compliance, reducing toxicity and lengths of hospital stay and enhancing the immune response.

The Value of Survival Gains in Pancreatic Cancer from Novel Treatment Regimens.

BACKGROUND: Metastatic pancreatic cancer (mPC) is associated with low survival, with less than 10% of patients surviving 5 years. Recent therapies improve survival outcomes where few alternative therapies exist, but few economic analyses measure the value of survival gains attributable to new therapies. OBJECTIVE: To estimate the value of survival gains in advanced or mPC attributable to the introduction of novel treatment regimens. METHODS: Multivariate Cox proportional hazards models were used to estimate real-world survival gains associated with the introduction of gemcitabine (GEM) for patients diagnosed with stage IV or unstaged mPC in the Surveillance, Epidemiology, and End Results Program cancer registries. Then, evidence from clinical trials was used to evaluate the survival gains associated with nab-paclitaxel + gemcitabine (nP +GEM) and FOLFIRINOX (FFX) relative to GEM. The survival estimates and clinical trial evidence were used to calibrate an economic model and assess the cumulative value of survival gains in mPC to patients. Costs of treatment were calculated based on published cost-effectiveness studies. RESULTS: We estimated that the introduction of GEM in 1996 was associated with a hazard ratio of 0.920 (P < 0.05) and an increase in median survival from 3.1 to 4.5 months. Results suggested that the value of survival gains attributable to GEM equaled about $71,000 per patient, while the value attributable to nP + GEM was an additional $56,700. Estimates for the value of survival gains per patient, net of total incremental lifetime treatment costs (drugs, adverse events, and other costs), were $50,294 for GEM and an additional $31,900 for nP + GEM. Clinical trials and cost-effectiveness studies reported an overall survival gain from FFX that was larger than, but statistically similar to, nP + GEM and had greater risk of adverse events and total incremental costs. We estimated that the total value of survival gains to mPC patients, net of total costs, associated with GEM was up to $47.6 billion, and the additional values attributable to nP+GEM and FFX were up to $39.0 billion and $26.3 billion, respectively. CONCLUSIONS: Historically, mPC patients have faced high disease burden and had few treatment options. Treatments introduced since 1996 have led to improved survival, with varying costs associated with treatment and adverse events. Accounting for total incremental costs, the majority of the value of survival gains from GEM and nP+GEM was retained by mPC patients, highlighting the value of innovation in settings where survival is low and few alternative therapies exist. DISCLOSURES: Support for this research was provided by Celgene. Precision Health Economics was compensated by Celgene for work on this study. MacEwan is an employee of, and Yin is a consultant to, Precision Health Economics. Kaura and Khan are employees of Celgene. Study concept and design were contributed primarily by Yin and MacEwan, along with Kaura and Khan. MacEwan collected the data, and data interpretation was performed primarily by MacEwan and Yin, along with Kaura and Khan. The manuscript was written and revised by MacEwan, Yin, Kaura, and Khan.

Population-Based Cost-Minimization Analysis of CAPOX Versus Modified FOLFOX6 in the Adjuvant Treatment of Stage III Colon Cancer.

BACKGROUND: Evidence suggests that CAPOX (capecitabine and oxaliplatin) has efficacy similar to 5-fluorouracil and oxaliplatin (mFOLFOX6) in the adjuvant treatment of colon cancer. CAPOX is partly administered orally and associated with a 3-week rather than a 2-week treatment cycle. A population-based cost-minimization analysis was conducted from the health care payer and societal perspectives to evaluate the potential cost savings of replacing mFOLFOX6 with CAPOX. METHODS: We applied treatment and toxicity data from phase III trials of CAPOX and FOLFOX-based regimens to the adjuvant colon cancer population in British Columbia, Canada. In this cost-minimization analysis we compared the total costs associated with chemotherapy medications, drug administration and delivery, hospital and clinic visits, treatment-related toxicities, and central venous access devices. Costs to patients in terms of lost time and travel were also considered. It was assumed that patients would receive either 8 cycles of CAPOX or 12 cycles of mFOLFOX6. RESULTS: From the payer perspective, the use of CAPOX resulted in cost savings of $5339 CAD per patient compared with the use of mFOLFOX6. From a societal perspective, CAPOX was also associated with savings of $6080 CAD per patient. The greatest cost savings with CAPOX were attributed to fewer visits for chemotherapy treatment and decreased central venous access device usage. CAPOX was also associated with reduced loss of time and decreased travel for patients because of the requirement of fewer clinic visits. CONCLUSIONS: Replacement of mFOLFOX6 with CAPOX in the adjuvant treatment of colon cancer might be associated with potential cost savings from the payer and societal perspectives.

Health economic changes as a result of implementation of targeted therapy for metastatic renal cell carcinoma: national results from DARENCA study 2.

BACKGROUND: Limited data exist on the economic consequences of implementing targeted therapy (TT) for metastatic renal cell carcinoma (RCC) in a real-world setting. OBJECTIVE: To analyze health care and productivity costs for TT implementation in a national cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: Costs were measured per patient per year during a 2-yr follow-up during 2002-2005 (immunotherapy only) and 2006-2009 (TT implementation). All Danish patients with a diagnosis code for RCC and a procedure code for TT or immunotherapy were linked to the Danish National Patient Registry (contains information on all contacts with primary and secondary health sector). Health care and productivity costs were retrieved from the Danish case-mix system and Coherent Social Statistics, respectively. Drug costs were calculated separately from procedure codes and retail prices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generalized linear models were used to analyze costs adjusted for age, gender, and civil status. RESULTS AND LIMITATIONS: A total of 439 patients were included for 2006-2009 and 192 for 2002-2005. Comparison of the health care cost per patient per year between 2006-2009 and 2002-2005 revealed lower inpatient costs (€11 899 vs €19 944, adjusted relative risk [RR] 0.64), higher outpatient costs (€14 308 vs €6209, RR 2.39), lower radiotherapy costs (€194 vs €633, RR 0.31), higher radiology costs (€676 vs €191, RR 3.73), and higher separately calculated drug costs (€12 040 vs €3103, RR 3.82, all p<0.001) for the former. Total health care costs per patient per year did not significantly differ (€27 676 vs €27 856, RR 1.05, p=0.5) between the two periods. Income from employment did not significantly differ between 2006-2009 and 2002-2005 (RR 1.11, p=0.11) and costs associated with loss of productivity were €7852 and €8265, respectively. CONCLUSIONS: A different pattern of health care costs were observed but total health care costs per patient per year did not significantly differ after implementation of TT for patients with mRCC. PATIENT SUMMARY: In this nationwide study, we found changes in the pattern of health care costs for patients with metastatic kidney cancer after implementation of targeted therapy compared to an immunotherapy control period; however, total health care costs and income from employment were without significant changes.

Health-related quality of life and cost comparison of adjuvant capecitabine versus 5-fluorouracil/leucovorin in stage III colorectal cancer patients.

PURPOSE: The purpose of this study was to compare health-related quality of life (HRQoL) and costs associated with 2 adjuvant chemotherapy regimens [capecitabine-based therapy versus 5-fluorouracil/leucovorin (5-FU/LV)-based therapy] in stage III colorectal cancer patients. METHODS: We conducted a prospective, open-label, observational, multicenter study from July 2008 to July 2011. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires was used to assess HRQoL before, during, and after treatment. The direct and indirect costs of adjuvant treatment were estimated from a specially prepared questionnaire, the National Health Insurance Research Database, and other published sources. We used propensity scoring to match samples between groups and performed multivariate analyses to adjust for differences in patient demographics and clinical characteristics. RESULTS: A total of 497 patients were enrolled, and 356 completed the surveys. Following propensity score matching, 239 patients were included in the analysis (122 in the capecitabine-based group, 117 in the 5-FU/LV-based group). Global HRQoL scores did not differ significantly between the two groups. However, compared to patients in the 5-FU/LV-based group, patients in the capecitabine-based group had less nausea and vomiting (mid-term, P = 0.024; final, P = 0.013), appetite loss (mid-term, P < 0.0001; final, P = 0.001), and fewer side effects from chemotherapy (mid-term, P = 0.017). In addition, the monthly cost of capecitabine-based therapy was lower than those of 5-FU/LV-based therapy [NT$31,895.46 (US$1063.18) vs. NT$79,159.24 (US$2638.64) per patient]. CONCLUSIONS: Capecitabine is a reasonable alternative and cost-effective treatment option under current conditions for patients with stage III colorectal cancer.

Cost-effectiveness analysis of colon cancer treatments from MOSIAC and No. 16968 trials.

AIM: To compare XELOX and FOLFOX4 as colon cancer adjuvant chemotherapy based on MOSAIC and No. 16968 trails from Chinese cost-effectiveness perspective. METHODS: A decision-analytic Markov model was developed to compare the FOLFOX4 and XELOX regimens based MOSAIC and No. 16968 trial. Five states were included in our Markov model: well (state 1), minor toxicity (state 2), major toxicity (state 3), quitting adjuvant chemotherapy (state 4), and death due to adjuvant chemotherapy (state 5). Transitions among the 5 states were assumed to be Markovian. Costs were calculated from the perspective of the Chinese health-care payer. The utility data were taken from published studies. Sensitivity analyses were used to explore the impact of uncertainty factors in this cost-effectiveness analysis. RESULTS: Total direct costs of FOLFOX4 and XELOX per patient were $19884.96 ± 4280.30 and $18113.25 ± 3122.20, respectively. The total fees related to adverse events per patient during the entire treatment were $204.75 ± 16.80 for the XELOX group, and $873.72 ± 27.60 for the FOLFOX4 group, and the costs for travel and absenteeism per patient were $18495.00 for the XELOX group and $21,352.68 for the FOLFOX4 group. The base-case analysis showed that FOLFOX4 was estimated to produce an additional 0.06 in quality adjusted life years (QALYs) at an additional cost of $3950.47 when compared to the XELOX regimen over the model time horizon. The cost per QALY gained was $8047.30 in the XELOX group, which was $900.98 less than in the FOLFOX4 group ($8948.28). The one way sensitivity analysis demonstrated that the utility for the well state and minor toxicity state greatly influenced the incremental cost-effectiveness ratio of FOLFOX4. CONCLUSION: In term of cost-comparison, XELOX is expected to dominate FOLFOX4 regimes; Therefore, XELOX provides a more cost-effective adjuvant chemotherapy for colon cancer patients in China.

Cost-effectiveness analysis of adjuvant chemotherapies in patients presenting with gastric cancer after D2 gastrectomy.

BACKGROUND: To analyze and compare the economic outcomes of adjuvant chemotherapy with capecitabine plus oxaliplatin (referred to as the XELOX strategy) and of S-1 (the S-1 strategy) for gastric cancer patients after D2 gastrectomy. METHODS: A Markov model was developed to simulate the lifetime disease course associated with stage II or III gastric cancer after D2 gastrectomy. The lifetime quality-adjusted life years (QALYs), associated costs, and incremental cost-effectiveness ratios (ICERs) were estimated. The clinical data were derived from the results of pilot studies. Direct costs were estimated from the perspective of the Chinese healthcare system, and the utility data were measured from end-point observations of Chinese patients. Sensitivity analyses were used to explore the impact of uncertainty on the model's outcomes. RESULTS: The combined adjuvant chemotherapy strategy with XELOX yielded the greatest increase in QALYs over the course of the disease (8.1 QALYs compared with 7.8 QALYs for the S-1 strategy and 6.2 for surgery alone). The incremental cost per QALY gained using the XELOX strategy was significantly lower than that for the S-1 strategy ($3,502 vs. $6,837, respectively). The results were sensitive to the costs of oxaliplatin and the hazard ratio of relapse-free survival. CONCLUSION: The observations reported herein suggest that adjuvant therapy with capecitabine plus oxaliplatin is a highly cost-effective strategy and more favorable treatment option than the S-1 strategy in patients with stage II or III gastric cancer who have undergone D2 gastrectomy.

Cost-effectiveness analysis of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

OBJECTIVE: To investigate the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil and leucovorin) compared with bevacizumab plus mFOLFOX6 in first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC). DESIGN: A semi-Markov model was constructed from a French health collective perspective, with health states related to first-line treatment (progression-free), disease progression with and without subsequent active treatment, resection of metastases, disease-free after successful resection and death. METHODS: Parametric survival analyses of patient-level progression-free and overall survival data from the only head-to-head clinical trial of panitumumab and bevacizumab (PEAK) were performed to estimate transitions to disease progression and death. 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 French 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 applied. Scenario, one-way, and probabilistic sensitivity analyses were performed. RESULTS: Based on a head-to-head clinical trial that demonstrates better efficacy outcomes for patients with wild-type RAS mCRC who receive panitumumab plus mFOLFOX6 versus bevacizumab plus mFOLFOX6, the incremental cost per life-year gained was estimated to be €26,918, and the incremental cost per quality-adjusted life year (QALY) gained was estimated to be €36,577. Sensitivity analyses indicate the model is robust to alternative parameters and assumptions. CONCLUSIONS: The incremental cost per QALY gained indicates that panitumumab plus mFOLFOX6 represents good value for money in comparison to bevacizumab plus mFOLFOX6 and, with a willingness-to-pay ranging from €40,000 to €60,000, can be considered cost-effective in first-line treatment of patients with wild-type RAS mCRC.

Cost-effectiveness of aspirin adjuvant therapy in early stage colorectal cancer in older patients.

BACKGROUND & AIMS: Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older. METHODS: Two five-state Markov models were constructed separately for Stage I and II colorectal cancer using TreeAge Pro 2014. Two hypothetical cohorts of 10,000 individuals at a starting age of 65 years and with colorectal cancer in remission were put through the models separately. Cost-effectiveness of aspirin was evaluated against no treatment (Stage I and II) and capecitabine (Stage II) over a 20-year period from the United States societal perspective. Extensive one-way sensitivity analyses and multivariable Probabilistic Sensitivity Analyses (PSA) were performed. RESULTS: In the base case analyses, aspirin was cheaper and more effective compared to other comparators in both stages. Sensitivity analyses showed that no treatment and capecitabine (Stage II only) can be cost-effective alternatives if the utility of taking aspirin is below 0.909, aspirin's annual fatal adverse event probability exceeds 0.57%, aspirin's relative risk of disease progression is 0.997 or more, or when capecitabine's relative risk of disease progression is less than 0.228. Probabilistic Sensitivity Analyses (PSA) further showed that aspirin could be cost-effective 50% to 80% of the time when the willingness-to-pay threshold was varied from USD 20,000 to USD 100,000. CONCLUSION: Even with a modest treatment benefit, aspirin is likely to be cost-effective in Stage I and II colorectal cancer, thus suggesting a potential unique role in secondary prevention in this group of patients.

Cost-utility analysis of the newly recommended adjuvant chemotherapy for resectable gastric cancer patients in the 2011 Chinese National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Gastric Cancer.

BACKGROUND: Postoperative adjuvant chemotherapy with capecitabine and oxaliplatin was first recommended for resectable gastric cancer patients in the 2011 Chinese National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Gastric Cancer, but the economic influence of this therapy in China is unknown. OBJECTIVE: The aim of the present study was to determine the cost-effectiveness of adjuvant chemotherapy with capecitabine and oxaliplatin after a gastrectomy with extended (D2) lymph-node dissection, compared with a D2 gastrectomy alone, for patients with stage II-IIIB gastric cancer. METHODS: On the basis of data from the CLASSIC trial, a Markov model was created to determine economic and clinical data for patients in the chemotherapy and surgery group (CSG) and the surgery-only group (SOG). The costs, presented in 2010 US dollars and estimated from the perspective of the Chinese health-care system, were obtained from the published literature and the local health system. The utilities were based on published literature. Costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were estimated. A lifetime horizon and a 3 % annual discount rate were used. One-way and probabilistic sensitivity analyses were performed. RESULTS: For the base case, the CSG compared with SOG would increase LYs and QALYs in a 3-, 5-, 10- or 30-year time horizon (except the QALYs at 3 or 5 years). In the short run (such as in 3 or 5 years), the medical costs would increase owing to adjuvant chemotherapy of capecitabine plus oxaliplatin after D2 gastrectomy, but in the long run the costs would decline. The ICERs suggested that the SOG was dominant at 3 or 5 years and the CSG was dominant at 10 or 30 years. The one-way sensitivity analysis showed that the utility of disease-free survival for 1-10 years for the SOG and the cost of oxaliplatin were the most influential parameters. The probabilistic sensitivity analysis predicted a 98.6 % likelihood that the ICER for the CSG would be less than US$13,527/QALY (three times the per capita gross domestic product of China). CONCLUSION: For patients in China with resectable disease, our results suggest that adjuvant chemotherapy with capecitabine plus oxaliplatin after a D2 gastrectomy is cost-saving and dominant in the long run on the basis of a current clinical trial, compared with treatment with a D2 gastrectomy alone.

Cost-Effectiveness Analysis of Adjuvant Stage III Colon Cancer Treatment at Veterans Affairs Medical Centers.

The objective of this study was to evaluate the real-world cost effectiveness of adjuvant stage III colon cancer chemotherapy regimens, given that previous analyses have been based on data from clinical trials. The study was designed using integrated decision tree and Markov model, which was developed to evaluate the cost effectiveness of 5-fluorouracil/leucovorin (5-FU/LV), capecitabine, and the combination of each with oxaliplatin. The analysis was performed from a US Veterans Affairs perspective via retrospectively collected data, over a 5-year model time horizon. Outcome and cost data were used to calculate cost per quality adjusted life year (QALY), and one-way and probabilistic sensitivity analyses were performed. In the base case analysis, capecitabine and capecitabine plus oxaliplatin both cost more and were less effective than other regimens, and 5-FU/LV plus oxaliplatin, compared to 5-FU/LV alone, resulted in a cost of $25,997 per QALY gained. Model results were generally robust to parameter variation. Capecitabine plus oxaliplatin could be economically reasonable if full dosing occurred ≥76% of the time (base case 42%). In a real-world setting, the addition of oxaliplatin to 5-FU/LV is more effective but also more costly than 5-FU/LV alone. If full dosing of capecitabine-containing regimens can be assured, they may also be cost-effective strategies.

Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

BACKGROUND: First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. OBJECTIVE: The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. METHODS: A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. RESULTS: For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. CONCLUSIONS: Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

[Chemotherapy in male external genital organs (testicular and penile cancer)]. / Chimiothérapie des organes génitaux externes chez l'homme (cancer du testicule et du pénis).

AIM: To describe drugs used in the chemotherapy of testis and penis neoplasms. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: Nowadays, the chemotherapy is perfectly codified in adjuvant treatment or in first-line treatment of metastatic testis cancer. A single dose of carboplatin for seminoma testicular (stage I) in adjuvant treatment situation is one of the latest advances. Concerning penis cancer, the optimal protocols validated by a high level of evidence are missing. CONCLUSION: The chemotherapy in testis and penis neoplasms knew few advances in recent years. So, it is necessary to include patients in clinical research protocols.