Cost Effectiveness of Pembrolizumab for Advanced Melanoma Treatment in Portugal.

BACKGROUND: The aim of this study was to assess the cost-effectiveness of pembrolizumab in treating patients with ipilimumab-naïve advanced melanoma in Portugal. METHODS: A cost-effectiveness model was developed to analyze the costs and consequences of treatment with pembrolizumab compared to treatment with ipilimumab in patients with advanced melanoma not previously treated with ipilimumab. The model was parameterized by using data from a head-to-head phase III randomized clinical trial, KEYNOTE-006. Extrapolation of long-term outcomes was based on approaches previously applied, combining ipilimumab data and melanoma patients' registry data. The analysis was conducted from the perspective of the Portuguese National Health Service, and a lifetime horizon (40 years) was used. Portugal-specific disease management costs were estimated by convening a panel of six clinical experts to derive health state resource use and multiplying the results by national unit costs. To test for the robustness of the conclusions, we conducted deterministic and probabilistic sensitivity analyses. RESULTS: Pembrolizumab increases life expectancy in 1.57 undiscounted life-years (LYs) and is associated with an increase in costs versus that of ipilimumab. The estimated incremental cost-effectiveness ratio is €47,221 per quality-adjusted life-year (QALY) and €42,956 per LY. Deterministic sensitivity analysis showed that the results were robust to the change of most input values or assumptions and were sensitive to time on treatment scenarios. According to the probabilistic sensitivity analysis performed, pembrolizumab is associated with a cost per QALY gained inferior to €50,000 in 75% of the cases. CONCLUSIONS: Considering the usually accepted thresholds in oncology, pembrolizumab is a cost-effective alternative for treating patients with advanced melanoma in Portugal.

Conceptual Framework and Methodological Challenges for Modeling Effectiveness in Oncology Treatment Sequence Models.

In this review, we summarize the challenges faced by existing oncology treatment sequence decision models and introduce a general framework to conceptualize such models. In the proposed framework, patients with cancer receive at least two lines of therapy (LOTs) followed by palliative care throughout their lifetime. Patients cycle through progression-free and progressive disease health states in each LOT before death. Under this framework, four broad aspects of modeling effectiveness of treatment sequences need exploration. First, disease progression, treatment discontinuation, and the relationship between the two events should be considered. Second, the effectiveness of each LOT depends on its placement in a treatment sequence as the effectiveness of later LOTs may be influenced by the earlier LOTs. Third, the treatment-free interval (TFI; time between discontinuation of earlier LOT and initiation of later LOT) may impact a therapy's effectiveness. Fourth, in the absence of head-to-head trials directly comparing LOTs, indirect treatment comparison (ITC) of outcomes for a specific LOT or even for the entire treatment sequence is important to consider. A search of decision models that estimated effectiveness of at least two lines of oncology therapy was conducted in PubMed (N = 20) and technology appraisals by the National Institute for Health and Care Excellence (N = 26) to assess four methodological aspects related to the model framework: (1) selection of outcomes for effectiveness in a treatment sequence, (2) approaches to adjust the efficacy of a treatment in consideration of its place in the sequence, (3) approaches to address TFIs between LOTs, and (4) incorporation of ITCs to estimate comparators' effectiveness in the absence of direct head-to-head evidence. Most models defined health states based on disease progression on different LOTs while estimating treatment duration outside of the main model framework (30/46) and used data from multiple data sources in different LOTs to model efficacy of a treatment sequence (41/46). No models adjusted efficacy for the characteristics of patients who switched from an earlier LOT to a later LOT or adjusted for the impact of prior therapies, and just six models considered TFIs. While 11 models applied ITC results to estimate efficacy in comparator treatment sequences, the majority limited the ITC to one LOT in the sequence. Thus, there is substantial room to improve the estimation of effectiveness for treatment sequences using existing data when comparing effectiveness of alternative treatment sequences.

Cost-effectiveness of Pembrolizumab as Second-line Therapy for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in Sweden.

BACKGROUND: Urothelial carcinoma (UC) is the most common subtype of bladder cancer. The randomized phase 3 KEYNOTE-045 trial showed that pembrolizumab, used as second-line therapy significantly prolonged overall survival with fewer treatment-related adverse events than chemotherapy for advanced UC. Pembrolizumab has been approved by the European Medicines Agency for the treatment of locally advanced or metastatic UC in adults who have received platinum-containing chemotherapy. Many European countries use cost-effectiveness analysis to inform reimbursement decisions. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab as second-line therapy for the treatment of advanced UC from a Swedish health care perspective. DESIGN, SETTING, AND PARTICIPANTS: We developed a partitioned-survival model to assess the costs and effectiveness of pembrolizumab compared with vinflunine (base case), paclitaxel, or docetaxel monotherapy in patients with advanced UC over a 15-yr time horizon. We obtained Kaplan-Meier estimates for survival endpoints, adverse events, and utility data from KEYNOTE-045. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed parametric extrapolations to estimate overall and progression-free survival beyond the clinical trial period. Swedish costs and utility weights were used to estimate total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We performed deterministic and probabilistic sensitivity analyses to assess the robustness of the model results. RESULTS AND LIMITATIONS: In the base-case analysis, pembrolizumab resulted in a mean survival gain of 1.66 years (1.38 QALYs) at an incremental cost of €69852 and an ICER of €50529/QALY gained versus vinflunine monotherapy. ICERs for other chemotherapies were €81356/QALY for pembrolizumab versus paclitaxel or docetaxel monotherapy, and €71924/QALY for pembrolizumab versus paclitaxel, docetaxel, or vinflunine monotherapy. Long-term follow-up from KEYNOTE-045 and real-world data are needed to validate the extrapolations. CONCLUSIONS: The results indicate that pembrolizumab improves survival, increases QALYs, and is cost-effective as second-line therapy at a willingness-to-pay threshold of €100000/QALY for the treatment of advanced UC. PATIENT SUMMARY: To date, pembrolizumab is the only treatment associated with a significant overall survival benefit compared with chemotherapy in a randomized controlled trial as second-line therapy for advanced urothelial carcinoma. Our trial-based cost-effectiveness analysis suggests that pembrolizumab is a cost-effective option over chemotherapy in patients with advanced urothelial carcinoma after platinum-based therapy in Sweden.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BACKGROUND: Pembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy. METHODS: The model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: The BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold. CONCLUSION: First-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.

Incremental 1-year medical resource utilization and costs for patients with herpes zoster from a set of US health plans.

BACKGROUND: Nearly 1 million new episodes of herpes zoster (HZ) occur annually in the US, yet little is known about the medical resource utilization (RU) and costs associated with HZ and its complications. OBJECTIVES: To describe the medical RU and cost burden of HZ in the first 90 days and the first year after diagnosis from the health insurer perspective and to stratify this burden for patients diagnosed with post-herpetic neuralgia (PHN) and those who are immunocompromised. In addition, this study explores costs from the societal perspective as a result of work loss in the first year after diagnosis. METHODS: The medical RU and cost data were obtained from the MarketScan Research Database for the years 1998-2003. This database contains inpatient, outpatient and prescription drug data for approximately 14 million individuals of all ages, covered under a variety of fee-for-service and capitated provider reimbursement arrangements, including those with Medicare and private insurance. The work loss estimates were based on the MarketScan Health and Productivity Management Database. Claims for services incurred between 1 January 1998 and 31 December 2003 were screened to identify a cohort of HZ patients based on the presence of at least one International Classification of Diseases, 9th Revision (ICD-9) diagnosis code 053.xx. Each patient was assigned an index date based on the earliest observed occurrence of an HZ diagnosis. A cohort of PHN patients was identified as a subset of the HZ cohort with ICD-9 codes 053.12, 053.13, 053.19 or 729.2x in the period of 90 days to 12 months after the index date. Multivariable regression was used to compare HZ cases with matched controls after adjusting for demographic characteristics, insurance status, co-morbidities and medical expenditure in the 6 months prior to diagnosis for each of the endpoints. Separate regression models were developed, in which age and immune status were stratified. All costs were adjusted to March 2008 values using the medical care component of the Consumer Price Index. The average per patient cost of all HZ cases was $US605 in the first 90 days after diagnosis and $US1052 at 1 year. For the subset with PHN, the average per patient cost of HZ at 1 year was $US3815. For the subset with an immunocompromising condition, the average HZ cost at 1 year was $US1745. The majority of the costs were the result of outpatient visits and prescription drugs. The subset of HZ cases that had both absence hour and short-term disability (STD) records available had 26.5 absence hours and 2.9 STD days. Healthcare utilization, medical care costs and work loss all increased with age for all HZ cases. Based on the results from the present study, the direct medical cost burden of HZ in the US is high, exceeding $US1000 per HZ patient. This direct medical cost may be nearly twice as high in immunocompromised patients and four times as high in the subset of HZ cases with PHN. The direct medical cost burden of HZ may exceed $US1 billion annually in the US. The majority of medical RU and cost burden is incurred by the elderly. Although many people with HZ may no longer be in the workforce, HZ does contribute to lost work time.

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer.

OBJECTIVES: Pembrolizumab monotherapy showed significantly longer overall survival and fewer treatment-related adverse events compared to chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1)-positive tumors in the first-line setting in KEYNOTE (KN)-024 and in those previously treated in KN010. The objective of this analysis was to assess the benefit-risk of pembrolizumab in terms of quality-adjusted survival amongst patients in these trials. METHODS: The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments. Survival time was partitioned into three health states: with toxicity before disease progression, without toxicity before disease progression, and disease progression until death. Health state utilities were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in the trials. Q-TWiST was calculated as the utility-weighted sum of the mean health state durations. Trial data analyzed included the primary analysis and subsequent data cutoffs. The base-case analysis was based on the most recent analysis of the trials. RESULTS: Patients randomized to pembrolizumab had 2.49 months greater Q-TWiST (P value < 0.001) compared to those randomized to platinum-based chemotherapy at a follow-up of 24 months in KN024, and 2.29 months greater Q-TWiST (P value < 0.001) compared to docetaxel over 30 months follow-up in KN010. Results across the trial analyses showed an increase in trend for the Q-TWiST improvement of pembrolizumab over time. CONCLUSIONS: Pembrolizumab showed significant improvement in Q-TWiST compared to chemotherapy in advanced or metastatic NSCLC in both previously untreated and treated patients. The benefits of pembrolizumab continued to accrue with longer follow-ups.

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy.

BACKGROUND: There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis. RESULTS AND LIMITATIONS: We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY. CONCLUSIONS: At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine. PATIENT SUMMARY: This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden.

Comparative costs of ertapenem and cefotetan as prophylaxis for elective colorectal surgery.

BACKGROUND AND PURPOSE: The costs of treating surgical site infections can be considerable. There is a cost associated with the prophylactic use of antibiotics; however, the use of prophylactic agents may reduce infection rates and lengths of stay, thus offsetting the overall treatment cost and potentially generating cost savings to hospitals. This project was intended to determine the potential cost impact of using ertapenem 1 g vs. cefotetan 2 g as prophylaxis for elective colorectal surgery. METHODS: Cost analysis using efficacy data from the PREVENT clinical trial and drug acquisition and total hospital costs in 2005 dollars from Premier's Perspective Comparative Database in patients > or = 18 year of age, evaluable at four weeks after elective surgery of the colon or rectum and prophylactic treatment with ertapenem (n = 338) or cefotetan (n = 334). The primary outcome measures were the rate of prophylactic drug failure and the difference between the ertapenem and cefotetan groups in costs related to and total hospital stay. Prophylactic failure was defined as a surgical site infection, unexplained antibiotic use, or anastomotic leak. RESULTS: Prophylactic failure occurred in 28.1% of the patients receiving ertapenem and 42.8% of those receiving cefotetan (p < 0.05). The most common prophylactic failure was surgical site infection: 18.3% for ertapenem, 31.1% for cefotetan, difference (95% confidence interval) -13.0% (-19.5, -6.5%) (p < 0.05). The mean +/- standard deviation length of stay for all patients, including prophylactic successes and failures, was 7.6 +/- 6.6 days for ertapenem and 8.7 +/- 9.5 days for cefotetan. The mean per-patient cost of prophylactic drugs and hospital room and board was $15,245 with ertapenem and $17,428 cefotetan, a net difference of -$2,181. CONCLUSIONS: Ertapenem used in prophylaxis for elective colorectal operations results in a lower rate of surgical site infection and a shorter average length of stay than cefotetan. The calculated net difference in prophylactic antibiotic drug and hospital costs represents a saving of $2,181 per patient with ertapenem relative to cefotetan.

The potential cost-effectiveness of vaccination against herpes zoster and post-herpetic neuralgia.

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of this study was to examine the cost-effectiveness of vaccination against HZ and PHN in Canada. A cohort model was developed to estimate the burden of HZ and the cost-effectiveness of HZ vaccination, using Canadian population-based data. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. The economic evaluation was conducted from the ministry of health perspective and 5% discounting was used for costs and benefits. In Canada (population = 30 million), we estimate that each year there are 130,000 new cases of HZ, 17,000 cases of PHN and 20 deaths. Most of the pain and suffering is borne by adults over the age of 60 years and is due to PHN. Vaccinating 65-year-olds (HZ efficacy = 63%, PHN efficacy = 67%, no waning, cost/course = $150) is estimated to cost $33,000 per QALY-gained (90% CrI: 19,000-63,000). Assuming the cost per course of HZ vaccination is $150, probabilistic sensitivity analysis suggest that vaccinating between 65 and 75 years of age will likely yield cost-effectiveness ratios below $40,000 per Quality-Adjusted Life-Year (QALY) gained, while vaccinating adults older than 75 years will yield ratios less than $70,000 per QALY-gained. These results are most sensitive to the duration of vaccine protection and the cost of vaccination. In conclusion, results suggest that vaccinating adults between the ages of 65 and 75 years is likely to be cost-effective and thus to be a judicious use of scarce health care resources.

Health outcomes and cost-effectiveness of aprepitant in outpatients receiving antiemetic prophylaxis for highly emetogenic chemotherapy in Germany.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer therapy. We aimed to determine outcomes associated with use of aprepitant in outpatients undergoing highly emetogenic chemotherapy in Germany from a patient's and payer's perspective. METHODS: A decision-analytic model compared an aprepitant regimen (aprepitant/ondansetron/dexamethasone) to a control regimen (ondansetron/dexamethasone) over a five days period. Clinical results and resource utilisation observed in aprepitant phase III clinical trials were assigned German unit cost data. RESULTS: Complete response over one chemotherapy cycle was observed in 68% of patients in the aprepitant group (N=514) compared to 48% of patients in the control group (N=518). Patients were estimated to have gained an equivalent of 15 additional hours of perfect health per cycle (0.63 quality-adjusted life days) with aprepitant-based regimen compared to control regimen. Cost per quality-adjusted life year gained with aprepitant was estimated at euro28,891. CONCLUSIONS: Aprepitant substantially improved CINV-related health outcomes in patients undergoing highly emetogenic chemotherapy. Incremental benefits materialised in a cost-effective fashion.

Acute/subacute herpes zoster: healthcare resource utilisation and costs in a group of US health plans.

BACKGROUND: Although there are estimated to be nearly 1 million cases of herpes zoster diagnosed in the US each year, the economic costs associated with herpes zoster in the US have not been well described. OBJECTIVE: To describe the healthcare resource utilisation and costs associated with physician-diagnosed acute/subacute herpes zoster, from a payer perspective, using a large US healthcare claims database. METHODS: Data for the period 2000-1 were obtained from the Medstat Marketscan healthcare claims database. The duration of acute/subacute herpes zoster was considered to include the 21 days preceding, and 90 days following, the initial herpes zoster diagnosis. Resource utilisation was examined for individuals with newly diagnosed acute/subacute herpes zoster (n = 8741) and compared, through regression analyses, with that observed for control individuals from the same population (n = 50,000). Similar analyses were conducted for costs; the costs included reflected healthcare payments from patients, insurers and other sources. Regression analyses controlled for demographics (age, gender), conditions that have been observed with greater frequency among patients with acute/subacute herpes zoster in prior studies (cancer, HIV infection, organ transplantation, other immunosuppressive conditions and therapies) and the number of billed services within each of seven categories of care that were potentially related to acute/subacute herpes zoster and that were utilised within the 30-180 days prior to the diagnosis for affected patients, and over an analogous period for controls. RESULTS: The acute/subacute phase of herpes zoster was estimated to result in an average of 1.7 (standard error [SE] 0.02) additional physician and hospital outpatient visits, 0.05 (SE 0.003) additional emergency room visits, 0.03 (SE 0.003) additional inpatient hospital admissions, 2.1 (SE 0.03) additional prescriptions filled and $US431 (SE 17.60) in additional healthcare costs per patient. Among patients with acute/subacute herpes zoster, 21.1% had a diagnosis code with a designation for a herpes zoster-related complication, and 9.4% had three or more outpatient visits with a diagnosis code for herpes zoster. The average estimated incremental costs per patient with acute/subacute disease increased with age, ranging from $US258 (SE 37.70) among patients aged < or =19 years to $US805 (SE 106.30) among those aged > or =80 years. The numbers of additional outpatient visits, inpatient admissions, prescriptions filled for pain medications and coded complications were also substantially higher among older than younger patients with acute/subacute herpes zoster. CONCLUSIONS: The management of acute/subacute herpes zoster was found to result in substantial healthcare costs, with outpatient care and prescription drugs comprising the majority of the cost burden. To more fully understand the overall cost of herpes zoster disease to society, future studies should examine the healthcare costs associated with post-herpetic neuralgia and productivity losses due to herpes zoster and post-herpetic neuralgia.

Cost Effectiveness of Pembrolizumab vs. Standard-of-Care Chemotherapy as First-Line Treatment for Metastatic NSCLC that Expresses High Levels of PD-L1 in the United States.

OBJECTIVES: Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. METHODS: We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years. Parametric models were fitted to Kaplan-Meier estimates of time on treatment, progression-free survival and overall survival from the KEYNOTE-024 randomized clinical trial (patients aged ≥18 years with stage IV NSCLC, TPS ≥50%, without epidermal growth factor receptor (EGFR)-activating mutations or anaplastic lymphoma kinase (ALK) translocations who received no prior systemic chemotherapy) and validated with long-term registry data. Quality-adjusted life-years (QALYs) were calculated based on EuroQoL-5 Dimensions (EQ-5D) utility data collected in the trial. Costs ($US, year 2016 values) for drug acquisition/administration, adverse events and clinical management were included. Costs and outcomes were discounted at 3% per year. A series of deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: In the base-case scenario, pembrolizumab resulted in an expected gain of 1.31 life-years (LYs) and 1.05 QALYs and an incremental cost of $US102,439 compared with SoC. The incremental cost per QALY gain was $US97,621/QALY and the incremental cost per LY gain was $US78,344/LY. CONCLUSIONS: Pembrolizumab is projected to be a cost-effective option compared with SoC platinum-based chemotherapy as first-line treatment in adults with metastatic NSCLC expressing high levels of PD-L1.

Cost-Effectiveness of Pembrolizumab Versus Ipilimumab in Ipilimumab-Naïve Patients with Advanced Melanoma in the United States.

BACKGROUND: Recent clinical trials have shown that pembrolizumab significantly prolonged progression-free survival and overall survival compared with ipilimumab in ipilimumab-naïve patients with unresectable or metastatic melanoma. However, there has been no published evidence on the cost-effectiveness of pembrolizumab for this indication. OBJECTIVE: To assess the long-term cost-effectiveness of pembrolizumab versus ipilimumab in ipilimumab-naïve patients with unresectable or meta-static melanoma from a U.S. integrated health system perspective. METHODS: A partitioned-survival model was developed, which divided overall survival time into progression-free survival and postprogression survival. The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab. Extrapolation of progression-free survival and overall survival beyond the clinical trial was based on parametric functions and literature data. The base-case time horizon was 20 years, and costs and health outcomes were discounted at a rate of 3% per year. Clinical data-including progression-free survival and overall survival data spanning a median follow-up time of 15 months, as well as quality of life and adverse event data from the ongoing KEYNOTE-006 trial-and cost data from public sources were used to populate the model. Costs included those of drug acquisition, treatment administration, adverse event management, and disease management of advanced melanoma. The incremental cost-effectiveness ratio (ICER) expressed as cost difference per quality-adjusted life-year (QALY) gained was the main outcome, and a series of sensitivity analyses were performed to test the robustness of the results. RESULTS: In the base case, pembrolizumab was projected to increase the life expectancy of U.S. patients with advanced melanoma by 1.14 years, corresponding to a gain of 0.79 discounted QALYs over ipilimumab. The model also projected an average increase of $63,680 in discounted perpatient costs of treatment with pembrolizumab versus ipilimumab. The corresponding ICER was $81,091 per QALY ($68,712 per life-year) over a 20-year time horizon. With $100,000 per QALY as the threshold, when input parameters were varied in deterministic one-way sensitivity analyses, the use of pembrolizumab was cost-effective relative to ipilimumab in most ranges. Further, in a comprehensive probabilistic sensitivity analysis, the ICER was cost-effective in 83% of the simulations. CONCLUSIONS: Compared with ipilimumab, pembrolizumab had higher expected QALYs and was cost-effective for the treatment of patients with unresectable or metastatic melanoma from a U.S. integrated health system perspective. DISCLOSURES: This study was supported by funding from Merck & Co., which reviewed and approved the manuscript before journal submission. Wang, Pellissier, Xu, Stevinson, and Liu are employees of, and own stock in, Merck & Co. Chmielowski has served as a paid consultant for Merck & Co. and received a consultant fee for clinical input in connection with this study. Chmielowski also reports receiving advisory board and speaker bureau fees from multiple major pharmaceutical companies. Wang led the modeling and writing of the manuscript. Chmielowski, Xu, Stevinson, and Pellissier contributed substantially to the modeling design and methodology. Liu led the data collection work and contributed substantially to writing the manuscript. In conducting the analysis and writing the manuscript, the authors followed Merck publication polices and the "cost-effectiveness analysis alongside clinical trials-good research practices and the CHEERS reporting format as recommended by the International Society for Pharmacoeconomics and Outcomes Research.

Cost-effectiveness of pembrolizumab versus docetaxel for the treatment of previously treated PD-L1 positive advanced NSCLC patients in the United States.

OBJECTIVES: This analysis aimed to evaluate the cost-effectiveness of pembrolizumab compared with docetaxel in patients with previously treated advanced non-squamous cell lung cancer (NSCLC) with PD-L1 positive tumors (total proportion score [TPS] ≥ 50%). The analysis was conducted from a US third-party payer perspective. METHODS: A partitioned-survival model was developed using data from patients from the KEYNOTE 010 clinical trial. The model used Kaplan-Meier (KM) estimates of progression-free survival (PFS) and overall survival (OS) from the trial for patients treated with either pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 with extrapolation based on fitted parametric functions and long-term registry data. Quality-adjusted life years (QALYs) were derived based on EQ-5D data from KEYNOTE 010 using a time to death approach. Costs of drug acquisition/administration, adverse event management, and clinical management of advanced NSCLC were included in the model. The base-case analysis used a time horizon of 20 years. Costs and health outcomes were discounted at a rate of 3% per year. A series of one-way and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Base case results project for PD-L1 positive (TPS ≥50%) patients treated with pembrolizumab a mean survival of 2.25 years. For docetaxel, a mean survival time of 1.07 years was estimated. Expected QALYs were 1.71 and 0.76 for pembrolizumab and docetaxel, respectively. The incremental cost per QALY gained with pembrolizumab vs docetaxel is $168,619/QALY, which is cost-effective in the US using a threshold of 3-times GDP per capita. Sensitivity analyses showed the results to be robust over plausible values of the majority of inputs. Results were most sensitive to extrapolation of overall survival. CONCLUSIONS: Pembrolizumab improves survival, increases QALYs, and can be considered as a cost-effective option compared to docetaxel in PD-L1 positive (TPS ≥50%) pre-treated advanced NSCLC patients in the US.

The incidence of herpes zoster in a United States administrative database.

BACKGROUND: Few recent studies have reported data on the incidence of herpes zoster (HZ) in U.S. general clinical practice. OBJECTIVE: To estimate the age- and sex-specific incidence of HZ among U.S. health plan enrollees. DESIGN: Data for the years 2000 to 2001 were obtained from the Medstat MarketScan database, containing health insurance enrollment and claims data from over 4 million U.S. individuals. Incident HZ cases were identified through HZ diagnosis codes on health care claims. The burden of HZ among high-risk individuals with recent care for cancer, HIV, or transplantation was examined in sub-analyses. Overall incidence rates were age- and sex-adjusted to the 2000 U.S. population. PARTICIPANTS: MarketScan U.S. health plan enrollees of all ages. MEASUREMENTS AND MAIN RESULTS: We identified 9,152 incident cases of HZ (3.2 per 1,000 person-years) (95% confidence interval [CI], 3.1 to 3.2 per 1,000). Annual HZ rates per 1,000 person-years were higher among females (3.8) than males (2.6) (P<.0001). HZ rates rose sharply with age, and were highest among individuals over age 80 (10.9 per 1,000 person-years) (95% CI, 10.2 to 11.6). The incidence of HZ per 1,000 person-years among patients with evidence of recent care for transplantation, HIV infection, or cancer (10.3) was greater than for individuals without recent care for these conditions (3.0) (P<.0001). CONCLUSIONS: The overall incidence of HZ reported in the present study was found to be similar to rates observed in U.S. analyses conducted 10 to 20 years earlier, after age- and sex-standardizing estimates from all studies to the 2000 U.S. population. The higher rate of HZ in females compared with males contrasts with prior U.S. studies.

Modeling the durability of ZOSTAVAX® vaccine efficacy in people ≥60 years of age.

Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.

An observational, retrospective, cohort study of dosing patterns for rofecoxib and celecoxib in the treatment of arthritis.

OBJECTIVE: This study assessed prescribing patterns for rofecoxib and celecoxib in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA), as well as differences in prescribing patterns across physician specialties. METHODS: This was an observational, retrospective, cohort study of a large, US pharmacy claims database. Eligible patients were initiating therapy with rofecoxib or celecoxib and had succeeds, equals 90 days' supply of medication, as well as > or =1 medical claim specific to OA or RA between June 1, 2000, and May 31, 2001. Analyses were stratified according to diagnosis, prescribing physician specialty, and patient demographics. The main outcome measure was mean daily usage (ie, mean daily dose [milligrams]; mean number of pills per day; and mean daily consumption [denoted as DACON], calculated as daily dose divided by most frequently prescribed strength). This was primarily a descriptive study. Tests of statistical significance were not performed because the large sample size would have rendered small differences significant. RESULTS: A total of 58,574 patients with OA (81.8% [n=47,935]) or RA (18.2% [n=10,639]) received 220,627 prescriptions for rofecoxib or celecoxib (47.7% [n=27, 924] and 52.3% [n=30, 650] of patients, respectively) during the study period. Overall, the most frequently prescribed strengths were rofecoxib 25 mg and celecoxib 200 mg. In both OA and RA, the most frequently prescribed mean daily dose of rofecoxib was 25 mg. In OA, the most frequently prescribed mean daily dose of celecoxib was 200 mg; in RA, it was 400 mg. Both pills per day and DACON were higher for celecoxib than rofecoxib. The DACON for rofecoxib was unrelated to physician specialty. Rheumatologists prescribed celecoxib at 20% to 40% higher mean daily doses than did primary care physicians, orthopedic specialists, or other specialists. Regardless of physician specialty, the DACON appeared higher for patients with RA than OA, for men than women, and for younger (aged <65 years) than older patients. CONCLUSIONS: In this analysis, relative to the most frequently prescribed strength, celecoxib-treated patients with OA and RA had higher DACONs than rofecoxib-treated OA and RA patients across all subgroups. These observations may have economic implications in terms of direct effects on cost and the need for formularies to consider overall use patterns in addition to pill costs. However, these conclusions are limited by lack of clinical information (other than an OA or RA diagnosis), inability to ascertain actual use, and potential for selection bias.

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis patients in the UK.

INTRODUCTION: The objective of this study was to evaluate the potential economic implications of using etoricoxib versus non-selective NSAID alternatives in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in the UK. STUDY DESIGN: Decision-analytical modelling was used to calculate the expected costs and consequences of the use of etoricoxib compared with non-selective NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), NSAIDs plus histamine H2 receptor antagonists and NSAIDs plus misoprostol over a continuous treatment period of 1 year. METHODS: The model considered direct medical costs from the perspective of the UK National Health Service (NHS) and used data from phase IIb and III clinical trials of etoricoxib to determine probabilities of gastrointestinal (GI) events. Model outcomes were defined as resource-consuming GI-related events, including clinically evident gastroduodenal perforations, symptomatic gastroduodenal ulcers, or upper GI bleeding (collectively, PUBs ['perforation, ulcers and/or bleeding']). Resource utilisation and costs (2002 values) for the treatment of OA and RA as well as GI events were based on published literature and information available from UK-specific sources. MAIN OUTCOME MEASURES AND RESULTS: The model suggests that etoricoxib is cost saving compared with non-selective NSAIDs plus PPIs or non-selective NSAIDs plus misoprostol. The model also suggests that etoricoxib is cost effective in terms of the incremental cost per QALY gained for non-selective NSAIDs alone (pound 19,766) and for non-selective NSAIDs plus H2 antagonists (pound 9350). The incremental cost of etoricoxib per PUB avoided was pound 12,446 versus non-selective NSAIDs alone and pound 6438 versus NSAIDs co-prescribed with H2 antagonists. For patients without the presence of specific GI risk factors (history of GI event, corticosteroid use or disability), etoricoxib may be cost effective for patients over age 56 years, assuming a cost-effectiveness threshold of pound 30,000 per QALY gained. Etoricoxib may also be cost effective in patients of all ages who had at least one specific GI risk factor. CONCLUSIONS: The model suggests, with its underlying assumptions and data, that etoricoxib is a cost-effective alternative to therapeutic regimens involving non-selective NSAIDs for OA or RA, from the UK NHS perspective. Etoricoxib may be cost saving and dominant over non-selective NSAIDs used together with a PPI or misoprostol. When compared with non-selective NSAIDs alone or non-selective NSAIDs co-prescribed with H2 antagonists, the incremental cost per QALY gained with use of etoricoxib was within the generally accepted threshold for cost effectiveness (less than pound 30,000 per QALY gained).

Economic analysis of aprepitant-containing regimen to prevent chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Hong Kong.

AIM: We aim to evaluate the cost effectiveness of aprepitant-containing regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) in Hong Kong. METHODS: Both cost-effectiveness and cost-utility analyses were conducted utilizing a decision-analytic model to measure the economic costs and clinical outcomes associated with the aprepitant-containing regimen versus a standard regimen in the prevention of CINV. Analyses were conducted on the basis of four published double-blind randomized clinical trials involving different usages of serotonin receptor antagonists. RESULTS: The use of aprepitant-containing regimens is associated with an improvement in quality-adjusted life years (QALYs) compared with non-aprepitant regimens. For cisplatin-based chemotherapy, the incremental cost per QALY gained is HKD 239,644 (1 USD approximates HKD 7.8) when ondansetron is administered on day 1 only. The incremental cost per QALY is HKD 440,950 when ondansetron is used on day 1 to 4. For anthracycline and cyclophosphamide chemotherapy, the aprepitant-containing regimen is associated with incremental cost of HKD 195,442 per QALY gained. Similar results were obtained when other 5HT3 receptor antagonists are used. The use of aprepitant was associated with higher cost of drug but lower costs of emesis-related management. With the cost-effectiveness threshold set at the World Health Organization endorsed criteria of three times gross domestic product (GDP) per capita (three times GDP per capita in Hong Kong in 2011 is HKD 798,078), the current analyses showed that the aprepitant-containing regimen was cost-effective. CONCLUSIONS: In patients undergoing HEC, the use of aprepitant as the anti-emetic is cost-effective in Hong Kong.

Cost-effectiveness of an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer in the UK.

PURPOSE: Prevention of chemotherapy-induced nausea and vomiting (CINV) remains an important goal for patients receiving chemotherapy. The objective of this study was to define, from the UK payer perspective, the cost-effectiveness of an antiemetic regimen using aprepitant, a selective neurokinin-1 receptor antagonist, for patients receiving chemotherapy for breast cancer. METHODS: A decision-analytic model was developed to compare an aprepitant regimen (aprepitant, ondansetron, and dexamethasone) with a standard UK antiemetic regimen (ondansetron, dexamethasone, and metoclopramide) for expected costs and health outcomes after single-day adjuvant chemotherapy for breast cancer. The model was populated with results from patients with breast cancer participating in a randomized trial of CINV preventative therapy for cycle 1 of single-day chemotherapy. RESULTS: During 5 days after chemotherapy, 64% of patients receiving the aprepitant regimen and 47% of those receiving the UK comparator regimen had a complete response to antiemetic therapy (no emesis and no rescue antiemetic therapy). A mean of £37.11 (78%) of the cost of aprepitant was offset by reduced health care resource utilization costs. The predicted gain in quality-adjusted lifeyears (QALYs) with the aprepitant regimen was 0.0048. The incremental cost effectiveness ratio (ICER) with aprepitant, relative to the UK comparator, was £10,847/QALY, which is well below the threshold commonly accepted in the UK of £20,000-£30,000/QALY. CONCLUSION: The results of this study suggest that aprepitant is cost-effective for preventing CINV associated with chemotherapy for patients with breast cancer in the UK health care setting.