***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Nivolumab was the first programmed death receptor 1 ( PD-1 ) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients . Objective To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in Engl and . Methods A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab , dabrafenib , and vemurafenib for BRAF mutation-positive patients . Covariate-adjusted parametric curves for time to progression , pre-progression survival , and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data . Indirect treatment comparisons between nivolumab , ipilimumab , and dacarbazine were informed by these covariate-adjusted parametric curves , controlling for differences in patient characteristics . Kaplan – Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib . Patient utilities and re source use data were based on trial data or the literature . Patients are assumed to receive nivolumab until there is no further clinical benefit , assumed to be the first of progressive disease , unacceptable toxicity , or 2 years of treatment . Results Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients , with incremental cost-effectiveness ratios of £ 24,483 and £ 17,362 per quality -adjusted life year , respectively . The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves . Conclusions Nivolumab is a cost-effective treatment for advanced melanoma patients in Engl and 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 r and omized 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 re source 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 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 r and omized 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 review ed and approved the manuscript before journal su bmi ssion . 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 practice s and the CHEERS reporting format as recommended by the International Society for Pharmacoeconomics and Outcomes Research Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17 % . R and omized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab ( PEM ) , nivolumab ( NIVO ) , and ipilumumab (IPI)-demonstrate improved patient outcomes , but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear . To inform policy makers about the value of these treatments , we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma . Material s and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs ( 2016 US$ ) and quality -adjusted life years ( QALYs ) for treatment sequences with first-line NIVO , IPI , NIVO + IPI , PEM every 2 weeks , and PEM every 3 weeks . Health states were defined for initial treatment , first and second progression , and death . Rates for drug discontinuation , frequency of adverse events , disease progression , and death obtained from r and omized phase III trials were used to determine the likelihood of transition between states . Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty . Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO , or IPI followed by NIVO . Compared with the first-line dacarbazine treatment strategy , NIVO followed by IPI produced an incremental cost effectiveness ratio of $ 90,871/QALY , and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $ 198,867/QALY . Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma , first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective , immune-based treatment strategies for metastatic melanoma 
    Output:
    
Changes to key parameters were unlikely to change the conclusions of the CEA when the cost-effectiveness threshold was considered .
When parameter inputs are not exactly aligned , conclusions may still be comparable across jurisdictions .