NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China.

OBJECTIVE: The cost-effectiveness of NUDT15 genetic testing-guided initial 6-mercaptopurine (6-MP) dosing in children with acute lymphoblastic leukemia (ALL) was evaluated. METHODS: A decision tree model was used to evaluate the cost to China's medical system per quality-adjusted life-year (QALY) gained and cost per case of severe leukopenia avoided of NUDT15 genetic testing using public clinical data. RESULTS: Genetic testing-guided initial 6-MP dosing reduced overall costs by $518.61, and prevented 0.221 cases of Grade III-IV leukopenia and increased QALY by 0.00136 per patient. Results were robust in one-way analyses and probabilistic sensitivity analyses. CONCLUSION: NUDT15 genetic testing prior to the initial administration of 6-MP in pediatric ALL patients in China is less expensive than standard dosing without genetic testing.

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.

Solitary serum methotrexate level 36 hours post high-dose methotrexate: A safe, efficacious, and cost-effective strategy to monitor methotrexate toxicities in childhood leukemia in resource-limited centers.

BACKGROUND: The standard practice during high-dose methotrexate (HD-MTX) in acute lymphoblastic leukemia (ALL) to mitigate toxicity is to serially monitor levels till serum MTX < 0.01 µmol/L. Most resource-limited centers lack in-house access to MTX levels, and therefore repeated monitoring is costly and cumbersome. We studied the efficacy and safety of "solitary 36 hours post HD-MTX levels (MTX36 )." PROCEDURE: This prospective observational study consecutively enrolled children with ALL receiving HD-MTX. Cycles with unavailable MTX36 and MTX36  > 10 µmol/L were excluded. HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. MTX36 were performed at other centers. Leucovorin was given in six hourly doses 36 hours post HD-MTX. Hydration was continued until the last dose of leucovorin. MTX toxicities, including change of creatinine from baseline at 36 hours (∆Cr36 ), were noted. Two groups depending on MTX36 (≤1 µmol/L vs > 1 µmol/L) received six versus eight doses of leucovorin, and toxicities were compared. RESULTS: Twenty-nine children with median age five years (1-11) who received 100 HD-MTX cycles with a median MTX dose of 3 g/m2 (2-5) were analyzed. The median MTX36 level was 1.165 µmol/L (0.1-7.32). Toxicities of HD-MTX (CTCAE-4.0): transaminitis-22%; creatinine elevation ≥ 1.25 times baseline-24%; cytopenias-16%; mucositis-17%; acute kidney injury (AKI)-6%. All toxicities were ≤CTCAE grade 3. Creatinine elevation, AKI, and mucositis were significantly higher in the group with higher MTX36 . There was no correlation (r = 0.3) between ∆Cr36 and MTX36 . MTX36 was thrice more economical than the standard protocol. CONCLUSION: MTX36 is a potential cost-effective, efficacious, and safe limited sample strategy to monitor HD-MTX, particularly in centers where in-house MTX levels are unavailable.

An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia.

Cytarabine, the 4-amino-1-(ß-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.

S-1 or gemcitabine adjuvant therapy in resected pancreatic cancer: a cost-effectiveness analysis based on the JASPAC-01 trial.

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer.Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty.Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters.Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

Cost-effectiveness analysis of utidelone plus capecitabine for metastatic breast cancer in China.

Objective: To estimate the cost-effectiveness of utidelone plus capecitabine therapy compared to capecitabine alone in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes treatment in the Chinese context and provide a reference for the marketing of utidelone in China. Methods: A Markov model was developed based on the NCT02253459 clinical trial to simulate the clinical course of patients with metastatic breast cancer who had received taxanes and anthracycline therapy. The quality-adjusted life years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) were then analyzed to evaluate the benefits. Two-parametric Weibull distribution was conducted to fit PFS and OS curves by using R. Sensitivity analyses were performed to evaluate the stability of the model designed. Results: The addition of utidelone increased the cost and QALYs by $13,370.25 and 0.1961, respectively, resulting in an increased ICER of $68,180.78 per QALY. The most sensitive influential parameter on ICER was the price of utidelone. At the threshold of willingness-to-pay (WTP) of $24,380 (3 per capita GDP of China), the cost of utidelone per 30 mg of less than $18.5, $33.7, and greater than $48.8 resulted in a 100%, 50%, and 0% possibility of cost-effectiveness, respectively. The addition of utidelone was not cost-effective when it was $115.4 per 30 mg-the price of its analog paclitaxel. In consideration of varied economics levels across China, cost-effectiveness could be achieved with the price of utidelone ranging from $5.2 to $35.9. Limitations: The survival curves extended beyond the follow-up time horizon, of which data were generated not from the real analyses but from our established two-parameter Weibull survival model. Conclusion: It is recommended that the price of utidelone would be less than $18.5 per 30 mg in order to obtain cost-effectiveness for metastatic breast cancer patients resistant to anthracyclines and taxanes treatment in China.

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.

Long-term Survival and Value of Chimeric Antigen Receptor T-Cell Therapy for Pediatric Patients With Relapsed or Refractory Leukemia.

Importance: Among children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia, the rate of 5-year disease-free survival is 10% to 20%. Approval of tisagenlecleucel, a chimeric antigen receptor T-cell therapy, represents a new and potentially curative treatment option. However, tisagenlecleucel is expensive, with a current list price of $475 000 per one-time administration. Objective: To estimate the long-term survival and value of tisagenlecleucel for children and young adults with B-cell acute lymphoblastic leukemia. Design, Setting, and Participants: In this cost-effectiveness analysis, a decision analytic model was designed to extrapolate trial evidence to a patient lifetime horizon. The survival evidence for the model was extracted from 3 studies: B2202 (enrolled patients from April 8, 2015, to November 23, 2016), B2205J (enrolled patients from August 14, 2014, to February 1, 2016), and B2101J (enrolled patients from March 15, 2012, to November 30, 2015). Long-term survival and outcomes of patients younger than 25 years with B-cell acute lymphoblastic leukemia that is refractory or in second or later relapse were derived using flexible parametric modeling from the direct extrapolation of event-free survival and overall survival curves. The published Kaplan-Meier curves were digitized from November 1, 2017, to November 30, 2017, using an algorithm to impute patient-level time-to-event data. Sensitivity and scenario analyses assessed uncertainty in the evidence and model assumptions to further bound the range of cost-effectiveness. Data were analyzed from December 1, 2017, to March 31, 2018. Interventions: The primary intervention of interest was tisagenlecleucel. The comparator of interest was the chemoimmunotherapeutic agent clofarabine. Main Outcomes and Measures: Model outcomes included life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. Results: Forty percent of patients initiating treatment with tisagenlecleucel are expected to be long-term survivors, or alive and responding to treatment after 5 years. Tisagenlecleucel had a total discounted cost of $667 000, with discounted life-years gained of 10.34 years and 9.28 QALYs gained. The clofarabine comparator had a total discounted cost of approximately $337 000, with discounted life-years gained of 2.43 years and 2.10 QALYs gained. This difference resulted in an incremental cost-effectiveness ratio of approximately $42 000 per life-year gained and approximately $46 000 per QALY gained for tisagenlecleucel vs clofarabine. These results were robust to probabilistic sensitivity analyses. Across scenario analyses that included more conservative assumptions regarding long-term relapse and survival, the incremental cost-effectiveness ratio ranged from $37 000 to $78 000 per QALY gained. Conclusions and Relevance: Tisagenlecleucel likely provides gains in survival and seems to be priced in alignment with these benefits. This study suggests that payers and innovators should develop novel payment models that reduce the risk and uncertainty around long-term value and provide safeguards to ensure high-value care.

[Comparative costs study between ready-to-administer bag of gemcitabine and production in reconstitution unit]. / Étude comparative de coûts entre les poches de gemcitabine prêtes à l'emploi et une fabrication en unité de reconstitution.

INTRODUCTION: Dose-banding is needed to rationalise cytotoxic drugs preparations. A new step was recently crossed: gemcitabine is the first molecule to be sold in ready-to-administer bag. What's the pharmaco-economic impact of gemcitabine ready-to-administer bags versus manufacturing in preparation unit? METHODS: A retrospective analysis of gemcitabine dosage prepared over three months permitted to explain our consumption of this drug, and by modelling, to characterize the good prescription interval for each dosage. Compared costs study assessed cost of medicine, preparation kit and preparation time. RESULTS: Over the study period, for 5%, 7.5% and 10% of deviation, respectively 67%, 75% and 76% of preparations were covered by standard doses. We chose 7.5% interval. The manufacturing cost of gemcitabine infusions is around 30,000€/year for vials with solution for infusion, 32,300€ for vials with powder, versus 67,300€ for ready-to-administer bag. Approximately 7.75minutes of pharmacy technician time would be saved by preparation. DISCUSSION: Ready-to-administer bags of gemcitabine allow relevant coverage of manufacturing doses. The annual extra cost would reach 37,200€ for our establishment. But, it can be justified by expected benefits: safer medication circuit, saving time of pharmacy technician….

Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Treatments for metastatic pancreatic cancer include monotherapy with gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin (CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the non-GEM combination FOLFIRINOX. Combination therapies have yielded better survival outcomes than GEM alone. A sponsor-independent economic evaluation of these regimens has not been conducted for USA. OBJECTIVE: The objective of this study was to estimate the cost utility and cost effectiveness of these regimens from the payer perspective for USA. METHODS: A three-state Markov model (progression-free, progressed disease, death) simulating the total costs and health outcomes (quality-adjusted life-years; life-years) was developed to estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX clinical data were obtained from trial and indirect estimates were obtained from network meta-analyses. Lifetime horizon and 3%/year discount rates were used. RESULTS: FOLFIRINOX was the most expensive regimen and GEM the least costly regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more effective in quality-adjusted life-years and life-years. Compared to GEM, the incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per additional quality-adjusted life-year, respectively; and the incremental cost-effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per additional life-year, respectively. A probabilistic sensitivity analysis confirmed the base-case analysis. CONCLUSIONS: This sponsor-independent economic evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM, but not CIS + GEM, were more expensive but also more effective than GEM alone in terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM regimen appears to be the most cost effective in USA at a willingness-to-pay threshold of US$200,000/quality-adjusted life-year.

Cost-Effectiveness Analysis of an Adherence-Promotion Intervention for Children With Leukemia: A Markov Model-Based Simulation.

Objective: Improving medication adherence among children with B-cell precursor acute lymphoblastic leukemia (B-ALL) has the potential to reduce relapse rates but requires an investment in resources. An economic evaluation is needed to understand the potential costs and benefits of delivering adherence-promotion interventions (APIs) as part of standard clinical care. Methods: A Markov decision analytic model was used to simulate the potential incremental cost-effectiveness per quality-adjusted life year (QALY) to be gained from an API for children with B-ALL in first continuous remission compared with treatment as usual (TAU, no intervention). Model parameter estimates were informed by previously published studies. The primary outcome was incremental cost (2015 US$) per QALY gained for API compared with TAU. Results: The model predicts the API to result in superior health outcomes (4.87 vs. 4.86 QALYs) and cost savings ($43,540.73 vs. $46,675.71) as compared with TAU, and simulations indicate that, across a range of plausible parameter estimates, there is a 95% chance that the API is more effective and less costly than TAU. The API was estimated to remain more effective and less costly than TAU in situations where the prevalence of nonadherence exceeds 32% and when API improves baseline adherence in at least 3% of patients. Conclusions: Providing APIs to children with B-ALL may improve health outcomes and save costs over a 6-year period.

Impact of topical fluorouracil cream on costs of treating keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis.

BACKGROUND: It is unknown whether treatment costs for keratinocyte carcinoma (KC) and actinic keratosis (AK) can be lowered by spending more on chemoprevention. OBJECTIVE: To examine the impact of 1-course treatment with topical fluorouracil (5-FU) on the face and ears on KC and AK treatment costs over 3 years. METHODS: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention trial compared the efficacy of topical 5-FU 5% with that of vehicle control cream for reducing KC risk. Trial data and administrative data on costs and utilization were analyzed to measure postrandomization encounters and treatment costs for KC and AK care. Adjusted models were used to test for statistically significant differences between treatment arms for number of treatment encounters and costs. RESULTS: One year after randomization, the control arm had a higher mean number of treatment encounters for squamous cell carcinoma (0.04) than the intervention arm (0.01) (P < .01). At 1 year, the intervention arm had lower treatment and dermatologic costs: $2106 (standard deviation, $2079) compared with $2444 (standard deviation, $2716) for the control patients (P = .02). After 3 years, the intervention arm incurred a cost of $771 less per patient. LIMITATIONS: Care not provided or paid for by the Department of Veterans Affairs was not included. Results may not be generalizable to other payers. CONCLUSION: We found significant cost savings for patients treated with 5-FU.

Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG's amendments to the company's cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company's base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000-£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem.

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG.

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

The Incidence and Health Care Resource Burden of the Myelodysplastic Syndromes in Patients in Whom First-Line Hypomethylating Agents Fail.

BACKGROUND: Although hypomethylating agents (HMAs) are effective and approved therapies for patients with myelodysplastic syndromes (MDS), many patients do not benefit from treatment, and nearly all ultimately stop responding to HMAs. The incidence and cost burden of HMA failure are unknown yet needed to appreciate the magnitude and significance of such failure. METHODS: We analyzed a de-identified dataset of over 5 million individuals with private health insurance in the U.S. to estimate MDS incidence, prevalence, and treatments. Based on MDS provider interviews, a conceptual model of MDS patient management was constructed to create a new, claims-relevant and drug development-relevant definition of HMA treatment failure. This algorithm was used to define resource encumbrance of MDS patients in whom HMA treatment failed. RESULTS: We estimated an MDS incidence rate of ∼70 cases per 100,000 enrollees per year and a prevalence of 155 cases per 100,000 enrollees. The proportion of MDS patients receiving HMA treatment was low (∼3%), and treatment was typically initiated within 1 year of the first MDS claim. Notably, HMA-treated individuals were older and had more comorbidities than the overall MDS cohort. Total health care costs of managing MDS patients after HMA failure were high (∼$77,000 during the first 6 months) and were driven primarily by non-pharmacy costs. CONCLUSION: This study quantifies for the first time the burden of significant unmet need in caring for MDS patients following HMA treatment failure. The Oncologist 2017;22:379-385Implications for Practice: U.S.-based treatment patterns among MDS patients demonstrate the significant clinical, financial, and health care burden associated with HMA failure and call for active therapies for this patient population.

Azacitidine for Treating Acute Myeloid Leukaemia with More Than 30 % Bone Marrow Blasts: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness data used in the company's economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: "Remission", "Non-remission", "Relapse/Progressive disease" and "Death". The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine compared with the CCR was £20,648 per quality-adjusted life-year (QALY) gained. In the probabilistic sensitivity analysis, the mean ICER was £17,423 per QALY. At the willingness-to-pay of £20,000, £30,000 and £50,000 per QALY, the probability of azacitidine being cost effective was 0.699, 0.908 and 0.996, respectively. The ERG identified a number of errors in Celgene's model and concluded that the results of the company's economic evaluation could not be considered robust. After amendments to Celgene's model, the base-case ICER was £273,308 per QALY gained. In the probabilistic sensitivity analysis, the mean ICER was £277,123 per QALY. At a willingness-to-pay of £100,000 per QALY, the probability of azacitidine being cost effective was less than 5 %. In all exploratory analyses conducted by the ERG, the ICER exceeded the NICE's cost-effectiveness threshold range of £20,000-30,000 per QALY. Given the evidence provided in the submission, azacitidine did not fulfil NICE's end-of-life criteria. After considering the analyses performed by the ERG and submissions from clinician and patient experts, the NICE Appraisal Committee did not recommend azacitidine for this indication.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

OBJECTIVES: Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens. METHODS: A cost effectiveness decision model was constructed with data from GOG 0174. Outcome was cost per first-line treatment success expressed in terms of incremental cost-effectiveness ratio (ICER). Front-line failures were assumed to receive cross-over single agent therapy, second line failures; multi-agent chemotherapy. GOG 0174 had no quality of life (QOL) evaluation, so equal QOL (utility 1.0) was assumed but varied in sensitivity analysis. A second exploratory model included 5-day and 8-day MTX regimens. RESULTS: Act-D ($18,505) was more expensive compared to weekly MTX ($8950) with an ICER of $56,215 per first-line treatment success compared to weekly MTX. Small decreases in QOL dramatically increased the ICER during sensitivity analysis. Models with multi-day MTX regimens were also more cost-effective than Act-D. If effectiveness was redefined as avoidance of multi-agent chemotherapy, weekly MTX was more effective. CONCLUSIONS: With a complete cure rate for low-risk GTN regardless of initial agent, our model supports provider hesitation toward first line Act-D for low risk GTN. While Act-D is more effective for first line treatment success, it is more costly, and does not decrease rate of multi-agent chemotherapy use.

Cost-effectiveness of treatments for high-risk myelodysplastic syndromes after failure of first-line hypomethylating agent therapy.

PURPOSE: To evaluate optimal salvage therapy in high-risk myelodysplastic syndromes patients who have failed a first-line hypomethylating agent (HMA) therapy, given that treatment choice is challenging. METHODS: Using published literature and expert opinion, we developed a Markov model to evaluate the cost-effectiveness of current treatments for patients who failed first-line HMA therapy. The model predicted costs, life years, quality-adjusted life years and incremental cost-effectiveness ratios. Sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. RESULTS: Supportive care was the least expensive option ($65,704/patient) with the shortest survival (0.48 years). Low- and high-intensity chemotherapies and hematopoietic cell transplantation increased survival and costs with incremental cost-effectiveness ratios of $108,808, 306,103 and 318,163/life year, respectively. Switching HMA was more costly and less efficacious than another treatment option, namely low-intensity chemotherapy. CONCLUSIONS: Subsequent treatments in myelodysplastic syndrome patients who failed first-line HMA significantly increase costs, while only providing marginal clinical benefit and substantially increasing treatment-related morbidities. Additional treatment options would benefit resource allocation, clinical decision-making and patient outcomes.