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BACKGROUND: The treatment landscape for advanced nonsmall cell lung cancer (NSCLC) has evolved from 2015 onward, since the introduction of immune checkpoint inhibitors (ICIs). Considering this shif...

Background Pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are approved advanced melanoma (AM) immunotherapies. To address limited health-related quality of life (QoL) real-world evidence with immunotherapies in AM, we compared QoL in AM patients receiving either treatment in clinical practice. Methods A prospective US observational study enrolled adult AM patients initiating first-line PEMBRO or IPI + NIVO between June 2017 and March 2018. Endpoints included the QLQ-C30 global health score (GHS) and EuroQol visual analog scale (EQ-VAS) scores. Mean changes were compared using repeated measures mixed-effects models and are presented covariate adjusted. Results 225 PEMBRO and 187 IPI + NIVO patients were enrolled. From baseline through week 24, PEMBRO was associated with 3.2 mean GHS score increase (95% CI 0.5, 5.9; p = .02), while no change was observed with IPI + NIVO; 0.2 (95% CI − 2.6, 3.0; p = 0.87). Among objective treatment-responders, GHS scores associated with PEMBRO increased 6.0 (95% CI 3.1, 8.8; p p = .01). In treatment non-responders, IPI + NIVO was associated with GHS/QoL deterioration of − 3.7 (95% CI − 6.8, − 0.6; p = .02), PEMBRO non-responders demonstrated no change; 0.7 (95% CI − 2.3, 3.7; p = 0.6). Between treatments, PEMBRO patients increased 2.6 greater in EQ-VAS (95% CI 0.6, 4.5; p = .01) vs IPI + NIVO at 24 weeks. Conclusions PEMBRO was associated with better 24-week QoL compared to IPI + NIVO in actual clinical practice settings. Real-world data has known limitations, but with further confirmation these results may have implications for treatment selection.

Vaccine efficacy is often assessed by counting disease cases in a clinical trial. A new quantitative framework proposed here (“PoDBAY,” Probability of Disease Bayesian Analysis), estimates vaccine efficacy (and confidence interval) using immune response biomarker data collected shortly after vaccination. Given a biomarker associated with protection, PoDBAY describes the relationship between biomarker and probability of disease as a sigmoid probability of disease (“PoD”) curve. The PoDBAY framework is illustrated using clinical trial simulations and with data for influenza, zoster, and dengue virus vaccines. The simulations demonstrate that PoDBAY efficacy estimation (which integrates the PoD and biomarker data), can be accurate and more precise than the standard (case-count) estimation, contributing to more sensitive and specific decisions than threshold-based correlate of protection or case-count-based methods. For all three vaccine examples, the PoD fit indicates a substantial association between the biomarkers and protection, and efficacy estimated by PoDBAY from relatively little immunogenicity data is predictive of the standard estimate of efficacy, demonstrating how PoDBAY can provide early assessments of vaccine efficacy. Methods like PoDBAY can help accelerate and economize vaccine development using an immunological predictor of protection. For example, in the current effort against the COVID-19 pandemic it might provide information to help prioritize (rank) candidates both earlier in a trial and earlier in development.

To estimate the budget impact of adding tepotinib to United States (US) health plans for treating adult patients with metastatic non-small cell lung cancer (mNSCLC) harboring mesenchymal-epithelial transition exon 14 (The base-case analysis was conducted from the perspective of a hypothetical Medicare plan of 1 million members. Scenarios were analysed for other US health plans. Treatments included tepotinib, capmatinib, crizotinib, and standard of care (SoC). Patients eligible for tepotinib were estimated from published epidemiological data and literature, and real-world evidence. Clinical inputs were derived from the phase II VISION trial, US prescribing information, and published literature. Tepotinib uptake and projected testing rates forIn the base-case, 38-65 patients were eligible for tepotinib each year over the three-year time horizon. The cumulative net budgetary impact of tepotinib was -$692,541 (-2.6%); $26,531,670 in the scenario without tepotinib and $25,839,129 in the scenario with tepotinib. A negligible net budget impact was observed per member per month (PMPM) at $0.2457 and $0.2393, respectively, before and after tepotinib's introduction. Results were most sensitive to variability in unit costs of capmatinib and tepotinib and their corresponding median treatment durations. Sensitivity and scenario analyses support the conclusion that introducing tepotinib will have minimal budgetary impact for Medicare health plans. Similar results were obtained for other US health plans.Assumptions and expert opinion were applied to address data gaps in key model inputs.The estimated budgetary impact of tepotinib for the treatment of adult patients with mNSCLC harboring

Background: The treatment (tx) landscape for patients (pts) with metastatic melanoma (MM) has changed dramatically from systemic chemotherapy (chemo) to novel therapies, including targeted therapies (TT) and immunotherapies (IO mono- and combination therapy) in recent years. Healthcare resource utilization (HCRU) and cost data are needed to further evaluate tx in a value-based healthcare system. The study aimed to describe HCRU and total cost of care among first line (1L) US MM pts treated with IO, TT, or chemo. Methods: A retrospective observational study was conducted using a U.S. claims database. Adults with ≥2 claims for melanoma and ≥1 claim for metastasis between January 1, 2012 and June 30, 2017 were identified. Pts had pharmacy and medical enrollment ≥6 months pre and ≥3 months post 1L tx start. Per pt per month (PPPM) HCRU and costs were calculated by 1L tx drug class: PD-1, CTLA-4, CTLA-4+PD-1, mono-TT, combo-TT, and chemo. Adjusted odds ratios (OR) for HCRU were estimated by logistic regressions, and adjusted costs were estimated by generalized linear models to control for differences in pt characteristics across groups. Results: Among 1,599 MM pts (255 PD-1, 555 CTLA-4, 88 CTLA-4+PD-1, 210 mono-TT, 102 combo-TT, 389 chemo), mean age ranged from 59–68 years across tx groups, and the majority was male (62%). Any hospitalization during 1L was less frequent among PD-1 (26%) compared to 35%–46% of all other groups (all PPConclusions: Hospitalizations represent an important healthcare resource for MM pts and were lowest among PD-1. Total monthly costs varied substantially across 1L regimens and were significantly lower in PD-1 compared to CTLA-4, CTLA-4+PD-1, and combo-TT. HCRU and costs differentiate 1L MM regimens.

Aims To estimate the budget impact of adding tepotinib to United States (US) health plans for treating adult patients with metastatic non-small cell lung cancer (mNSCLC) harboring mesenchymal-epithelial transition exon 14 (METex14) skipping alterations. Methods The base-case analysis was conducted from the perspective of a hypothetical Medicare plan of 1 million members. Scenarios were analysed for other US health plans. Treatments included tepotinib, capmatinib, crizotinib, and standard of care (SoC). Patients eligible for tepotinib were estimated from published epidemiological data and literature, and real-world evidence. Clinical inputs were derived from the phase II VISION trial, US prescribing information, and published literature. Tepotinib uptake and projected testing rates for METex14 skipping alterations were based on market research. Unit costs (2020 US dollars [USD]) and resource utilization associated with drug acquisition and administration, treatment monitoring, disease and adverse event (AE) management, and subsequent treatment were derived primarily from public sources. Results In the base-case, 38-65 patients were eligible for tepotinib each year over the three-year time horizon. The cumulative net budgetary impact of tepotinib was -$692,541 (-2.6%); $26,531,670 in the scenario without tepotinib and $25,839,129 in the scenario with tepotinib. A negligible net budget impact was observed per member per month (PMPM) at $0.2457 and $0.2393, respectively, before and after tepotinib's introduction. Results were most sensitive to variability in unit costs of capmatinib and tepotinib and their corresponding median treatment durations. Sensitivity and scenario analyses support the conclusion that introducing tepotinib will have minimal budgetary impact for Medicare health plans. Similar results were obtained for other US health plans. Limitations Assumptions and expert opinion were applied to address data gaps in key model inputs. Conclusions The estimated budgetary impact of tepotinib for the treatment of adult patients with mNSCLC harboring METex14 skipping alterations is minimal from the perspective of US health plans.

Background We investigated the association between adverse events (AEs) suspected to be immune‐related and health care resource utilization, costs, and mortality among patients receiving programmed cell death 1/programmed cell death ligand 1 immune checkpoint inhibitor (ICI) monotherapy for urothelial carcinoma, renal cell carcinoma, non‐small cell lung cancer, or Merkel cell carcinoma. Patients and Methods We conducted a retrospective cohort study using medical and pharmacy claims and enrollment information from U.S. commercial and Medicare Advantage with Part D enrollees in the Optum Research Database from March 1, 2014, through April 30, 2019. Claims were linked with mortality data from the Social Security Death Index and the National Death Index. Eligible patients had at least one ICI claim between September 1, 2014, and April 30, 2019. Results After adjusting for potential confounding variables, we found patients with AEs had more than double the risk of an inpatient stay (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.9–2.5) and an 80% higher risk of an emergency visit (HR, 1.8; 95% CI, 1.6–2.1) than patients without AEs. Adjusted 6‐month total costs were $24,301 higher among patients with an AE versus those without ($99,037 vs. $74,736; 95% CI, $18,828–29,774; p, This article reports on the association between immune‐related adverse events and health care resource utilization, costs, and mortality among patients receiving PD‐1/PD‐L1 immune checkpoint inhibitor monotherapy for urothelial carcinoma, renal cell carcinoma, non‐small cell lung cancer, or Merkel cell carcinoma.

OBJECTIVE: This study examines European decision makers' consideration and use of quantitative preference data.; METHODS: The study reviewed quantitative preference data usage in 31 European countries to support marketing authorization, reimbursement, or pricing decisions. Use was defined as: agency guidance on preference data use, sponsor submission of preference data, or decision-maker collection of preference data. The data could be collected from any stakeholder using any method that generated quantitative estimates of preferences. Data were collected through: (1) documentary evidence identified through a literature and regulatory websites review, and via key opinion leader outreach; and (2) a survey of staff working for agencies that support or make healthcare technology decisions.; RESULTS: Preference data utilization was identified in 22 countries and at a European level. The most prevalent use (19 countries) was citizen preferences, collected using time-trade off or standard gamble methods to inform health state utility estimation. Preference data was also used to: (1) value other impact on patients, (2) incorporate non-health factors into reimbursement decisions, and (3) estimate opportunity cost. Pilot projects were identified (6 countries and at a European level), with a focus on multi-criteria decision analysis methods and choice-based methods to elicit patient preferences.; CONCLUSION: While quantitative preference data support reimbursement and pricing decisions in most European countries, there was no utilization evidence in European-level marketing authorization decisions. While there are commonalities, a diversity of usage was identified between jurisdictions. Pilots suggest the potential for greater use of preference data, and for alignment between decision makers. Copyright © 2020 ISPOR-The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.

The programmed death-1 inhibitor pembrolizumab has demonstrated efficacy and safety in clinical trials for treating advanced (unresectable/metastatic) melanoma. We investigated the real-world utilization of pembrolizumab and associated patient outcomes for advanced melanoma in US community oncology practices. This retrospective, observational study used deidentified data from electronic health records for adult patients with advanced melanoma who received pembrolizumab at The US Oncology Network sites from September 2014 through December 2015, with follow-up through September 2016. Patients enrolled in clinical trials were excluded. Overall survival (OS) and physician-stated progression-free survival (PFS) were analyzed from pembrolizumab initiation using Kaplan-Meier, and associations between pembrolizumab therapy and OS/PFS, using multivariable Cox regression. Of 168 patients studied, 110 (65%) were male; the median age was 66 years (range, 26-over 90). Pembrolizumab was prescribed as first-line, second-line, and third-line/later for 39 (23%), 87 (52%), and 42 (25%) patients, respectively. In total, 41 patients (24%) had brain metastases. At pembrolizumab initiation, 21/129 (16%) had Eastern Cooperative Oncology Group performance status (ECOG PS) >1; 51/116 (44%) had elevated lactate dehydrogenase. Median follow-up was 10.5 months (range, 0-25.1); median OS was 19.4 months (95% confidence interval, 14.0-not reached); median PFS was 4.2 months (95% confidence interval, 2.9-5.3). Brain metastases, ECOG PS>1, elevated lactate dehydrogenase, and third-line/later (vs. first-line) pembrolizumab were significant predictors (P

319 Background: To complement the clinical findings, utilities were analyzed based on patient-reported outcomes (PROs) from VISION trial (Cohort A; data cut: July 1, 2020), a Phase II trial showed durable clinical activity of tepotinib in advanced NSCLC METex14+. Methods: The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaires were completed at Day 1, every 6 weeks for 9 months, then every 12 weeks, for up to 30 days after the last tepotinib dose. The Quality of Life Utility Measure-Core 10 dimensions (QLE-C10D) and EQ-5D-5L utilities were derived using the utility algorithm from published literature and the US crosswalk, respectively. Utilities are preference-based, health-related quality of life (HRQoL) metrics expressed on a scale including 0 (dead) and 1 (full health). Linear mixed regression models were used to analyze utilities at baseline, pre-progression, and post-progression, and to understand the relationship between EQ-5D and QLE-C10D. Utilities were assessed by both independent review committee (IRC) and investigators. Results: Utilities were estimated for 150 of 152 pts, with 983 observations for EORTC and 907 for EQ-5D. Mean EORTC utilities increased after tepotinib initiation, from 0.691 at baseline to 0.722 in the IRC-assessed progression-free period, and decreased after progression (0.671). Consistent trends were identified when progression was based on investigator's assessment. Analyses of EQ-5D utilities yielded similar findings and utilities. The two questionnaires were generally highly correlated (Table). Prior treatment (yes/no; p=0.554), adenocarcinoma (p=0.881), or squamous histology (p=0.841) were not statistically significant predictors of EQ-5D utility, while progression status significantly predicted utility in all progression-based models (p≤0.002). Conclusions: VISION is the first trial of a MET inhibitor to provide data on PROs and utilities in NSCLC harboring METex14 skipping mutation. EORTC and EQ-5D (minimally important difference: 0.08) utilities show an increase in HRQoL from baseline during tepotinib treatment until progression. Utility with tepotinib did not vary by prior treatment status or histology. Clinical trial information: NCT02864992. [Table: see text]

Frank Xiaoqing Liu,1 Edward A Witt,2 Scot Ebbinghaus,1 Grace DiBonaventura Beyer,2 Reshma Shinde,1 Enrique Basurto,2 Richard W Joseph3 1Merck & Co., Inc., Kenilworth, NJ, USA; 2Kantar Health, New York, NY, USA; 3Mayo Clinic, Jacksonville, FL, USA Purpose: To examine and compare patient and oncologist preferences for advanced melanoma treatment attributes and to document their trade-offs for benefits with risks. Materials and methods: A discrete choice experiment (DCE) was conducted among advanced melanoma patients and oncologists. Qualitative pilot testing was used to inform the DCE design. A series of scenarios asked stakeholders to choose between two hypothetical medications, each with seven attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (MDT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to determine patients’ and oncologists’ choice-based preferences, analysis of variance models were used to estimate the relative importance of attributes, and independent t-tests were used to compare relative importance estimates between stakeholders. Results: In total, 200 patients and 226 oncologists completed the study. OS was most important to patients (33%), followed by AEs (29%) and ORR (25%). For oncologists, AEs were most important (49%), followed by OS (34%) and ORR (12%). An improvement from 55% to 75% in 1-year OS was valued similar in magnitude to a 23% decrease (from 55% to 32%) in likelihood of AEs for oncologists.Conclusion: Patients valued OS, AEs, and ORR sequentially as the most important attributes in making a treatment decision, whereas oncologists valued AEs most, followed by OS and ORR. In comparison, patients differed significantly from oncologists on the importance of ORR, AEs, and PFS, but were consistent in OS and the rest of attributes. Keywords: unresectable, metastatic melanoma, systemic therapy, discrete choice experiment&nbsp

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. Electronic supplementary material The online version of this article (doi:10.1007/s40273-017-0527-z) contains supplementary material, which is available to authorized users.

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.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.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.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.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.This study was supported by funding from MerckCo., which reviewed and approved the manuscript before journal submission. Wang, Pellissier, Xu, Stevinson, and Liu are employees of, and own stock in, MerckCo. Chmielowski has served as a paid consultant for MerckCo. 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.

Background: Both pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are FDA-approved immunotherapy regimens for advanced melanoma (AM). Each regimen has different toxicity profiles pote...

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US ...

The treatment landscape for patients with metastatic melanoma has changed dramatically with the introduction of novel therapies, such as targeted therapies and immunotherapies, in recent years. Health care resource utilization (HCRU) and cost data are needed to further evaluate these treatments in a value-based health care system.To examine HCRU and total cost of care among U.S. metastatic melanoma patients treated with first-line systemic therapies, including immunotherapies, targeted therapies, and chemotherapy.A retrospective observational study was conducted using a U.S. claims database. Adults with ≥ 2 claims for melanoma and ≥ 1 claim for metastasis between January 1, 2012, and June 30, 2017, were identified. Patients had pharmacy and medical enrollment ≥ 6 months before and ≥ 3 months following first-line treatment start. Per patient per month (PPPM) HCRU and costs were calculated by first-line treatment drug class: PD-1 inhibitors, CTLA-4 inhibitors, CTLA-4 + PD-1 combination, BRAF monotherapy, BRAF + MEK combination, and chemotherapy. Adjusted odds ratios (ORs) for HCRU were estimated by logistic regressions and adjusted costs were estimated by generalized linear models using log-link with gamma distribution to control for differences in patient characteristics across groups.Among 1,599 metastatic melanoma patients (PD-1, n = 255; CTLA-4, n = 555; CTLA-4 + PD-1, n = 88; BRAF, n = 210; BRAF + MEK, n=102; chemotherapy=389), mean age ranged from 59-68 years, and the majority were male (62%). Any hospitalization during first-line treatment was less frequent among PD-1-treated patients (25.9%) compared with 34.7%-45.5% of all other groups (allHospitalizations and ED visits represent important HCRU for metastatic melanoma patients and were lowest among PD-1-treated patients compared with any other systemic therapies (except for ED visits when compared with BRAF + MEK). Total monthly costs varied substantially across first-line regimens and were significantly lower in PD-1-treated patients compared with patients treated with CTLA-4, CTLA-4 + PD-1, and BRAF + MEK.This study was funded by Merck SharpDohme, a subsidiary of MerckCo. Klink, Feinberg, and Nero are employees of Cardinal Health Specialty Solutions, which received funding from Merck to conduct this study. Chmielsowki is a consultant to Merck but received no funding for the development of this manuscript. Ahsan and Liu are employees of Merck. Chmielowski reports advisory board/speaker fees from Bristol-Myers Squibb, Merck, Genentech/Roche, Iovance Biotherapeutics, HUYA Bioscience International, Compugen, Array BioPharma, Regeneron, Biothera, Janssen, and Novartis. Ahsan has a patent (US20160008380A1) pending.

Test-then-pool is a simple statistical method that borrows historical information to improve efficiency of the drug development process. The original test-then-pool method examines the difference between the historical and current information and then pools the information if there is no significant difference. One drawback of this method is that a nonsignificant difference may not always imply consistency between the historical and current information. As a result, the original test-then-pool method is more likely to incorrectly borrow information from the historical control when the current trial has a small sample size. Statistically, it is more natural to use an equivalence test for examining the consistency. This manuscript develops an equivalence-based test-then-pool method for a continuous endpoint, explains the relationship between the two test-then-pool methods, explores the choice of an equivalence margin through the overlap probability, and proposes an adjustment to the nominal testing level for controlling type I error under the true consistency scenario. Furthermore, the analytical forms of the type I error and power for the two test-then-pool methods are derived, and practical considerations for using them are presented.

Objective: To determine the efficacy of pembrolizumab relative to other treatments used in stage III melanoma by conducting a systematic literature review (SLR) and network meta-analysis (NMA). Methods: A SLR was conducted to identify randomized clinical trials (RCTs) evaluating approved adjuvant treatments including interferon-containing regimens, BRAF-inhibitors, and PD-L1 inhibitors in stage III melanoma patients. Relative treatment effects for recurrence-free survival (RFS) were synthesized with Bayesian NMA models that allowed for hazard ratios (HRs) to vary over time. Results: Included studies formed a connected network of evidence composed of eight trials. In high-risk stage III patients, the HR for pembrolizumab vs observation decreased significantly over time with the superiority of pembrolizumab over observation becoming statistically meaningful before 3 months. By 9 months, the HR for pembrolizumab vs observation was statistically significantly lower than the HR for most other treatments vs observation, with the exception of ipilimumab and biochemotherapy due to overlapping 95% credible intervals. In BRAF + patients, pembrolizumab was statistically significantly better than observation after 3 months. The HR for both BRAF-inhibitors vs observation increased significantly over time and pembrolizumab was statistically superior to both BRAF-inhibitors after 15 months. Conclusions: Pembrolizumab results in statistically significantly improved RFS compared to all competing regimens after 9 months, except ipilimumab and biochemotherapy, for the adjuvant treatment of stage III melanoma. However, point estimate HRs vs observation for pembrolizumab are much lower than those for ipilimumab. In BRAF + patients, the advantage of pembrolizumab versus competing interventions increases over time with respect to RFS.

e21108 Background: MET exon 14 ( METex14) skipping is found in approximately 3% of the non-small cell lung cancer (NSCLC) population and is associated with poor prognoses. We estimated the financial impact to US Medicare and commercial plans of reimbursing the receptor tyrosine kinase inhibitor (TKI) tepotinib for adult patients with metastatic NSCLC bearing METex14 skipping. Methods: We developed an Excel-based economic model to project plan financial outlays with or without tepotinib from 2021-2023. The number of patients eligible for treatment with MET TKIs was estimated from epidemiological data, real-world evidence, and forecasted biomarker testing rates. It was assumed this population has access to other TKIs (capmatinib and crizotinib) and non-targeted standards of care, including immune checkpoint inhibitors, anti–vascular endothelial growth factor (VEGF) medications, and chemotherapy. It was also assumed most patients receiving tepotinib would otherwise be treated with another TKI. Efficacy and safety inputs were obtained from the Phase II VISION study (July 2020 data cut-off), published literature and prescribing information. Resource utilization and costs (2020 US dollars) were informed by online pricing databases, CMS fee schedules, Healthcare Cost and Utilization Project (HCUP) and trial data, expert opinion, and publicly available sources. Results: In hypothetical Medicare and commercial plans with one million members each, an estimated 160 and 32 adult patients with metastatic NSCLC would test positive for METex14 skipping between 2021-2023, respectively. Of these, 26 Medicare and 5 commercial plan members would receive tepotinib. Introducing tepotinib reduced cumulative financial outlays by $661,379 and $151,700 for Medicare and commercial payers respectively, or $0.0061 and $0.0014 per patient per month, primarily due to lower overall drug acquisition and disease management costs relative to a treatment mix without tepotinib. Results are most sensitive to the clinical efficacy of tepotinib and capmatinib. Conclusions: Using tepotinib in adult patients with metastatic NSCLC bearing METex14 skipping is expected to have minimal financial impact on Medicare and commercial payers in the US.[Table: see text]

In the Netherlands, the current standard of care for treating patients with end-stage renal disease is three sessions of in-center hemodialysis (conventional ICHD). However, the literature indicates that high dose hemodialysis (high dose HD) may provide better health outcome such as survival and quality of life. The objective of this study was to determine the cost-effectiveness of high dose HD, both in-center and at home, in comparison to conventional ICHD from a Dutch payer's perspective over a 5 year period. Additionally, the cost-effectiveness of conventional HD at home in comparison to conventional ICHD will be analysed.A Markov model was developed assuming 28-day treatment cycles and was populated with data from Dutch and international renal registries, official tariffs and medical literature. Univariable and probabilistic sensitivity analyses were performed to test the robustness of the results.Using publicly available tariffs from the Dutch Healthcare Authority (Nederlandse Zorgautoriteit) of 2015, doing high dose ICHD instead of conventional ICHD shows an incremental cost-effectiveness ratio (ICER) of €275,747 per quality-adjusted life year (QALY) gained. In contrast, the ICER of high dose HD at home in comparison to conventional ICHD is €3248 per gained QALY. The final analysis shows that conventional HD at home is less costly per patient (-€3063) than conventional ICHD and results in health benefit improvement (+0.249 QALYs), and is therefore regarded as cost saving.Treating dialysis patients with conventional HD at home shows to be cost saving in comparison to conventional ICHD. However, the magnitude of clinical benefit of high dose HD at home is over two times greater than the clinical benefit of conventional HD at home. According to our analysis, from a payer's perspective, high dose HD should be offered as a home therapy to obtain its clinical benefits in a cost-effective manner. Future research should consider our findings alongside societal factors, such as patient preference, monitoring cost for the home patient, productivity loss and capacity.Baxter BV, The Netherlands.

Objectives To investigate the 5-year health care budget impact of variable distribution of adult patients treated with peritoneal dialysis (PD) and in-center hemodialysis (ICHD) on government funding in Malaysia. Methods An Excel-based budget impact model was constructed to assess dialysis-associated costs when changing dialysis modalities between PD and ICHD. The model incorporates the current modality distribution and accounts for Malaysian government dialysis payments and erythropoiesis-stimulating agent costs. Epidemiological data including dialysis prevalence, incidence, mortality, and transplant rates from the Malaysian renal registry reports were used to estimate the dialysis patient population for the next 5 years. The baseline scenario assumed a stable distribution of PD (8%) and ICHD (92%) over 5 years. Alternative scenarios included the prevalence of PD increasing by 2.5%, 5.0%, and 7.5% or decreasing 1% yearly over 5 years. All four scenarios were accompanied with commensurate changes in ICHD. Results Under the current best available cost information, an increase in the prevalent PD population from 8% in 2014 to 18%, 28%, or 38% in 2018 is predicted to result in 5-year cumulative savings of Ringgit Malaysia (RM) 7.98 million, RM15.96 million, and RM23.93 million, respectively, for the Malaysian government. If the prevalent PD population were to decrease from 8% in 2014 to 4.0% by 2018, the total expenditure for dialysis treatments would increase by RM3.19 million over the next 5 years. Conclusions Under the current cost information associated with PD and HD paid by the Malaysian government, increasing the proportion of patients on PD could potentially reduce dialysis-associated costs in Malaysia.

e17079 Background: Previous research has indicated a high burden of illness among mRCC pts who progressed to second line (2L) systemic therapy, suggesting benefits to delaying 1L progression. This study examined the clinical impact of early vs delayed disease progression among mRCC pts treated with 1L TKI monotherapies followed by 2L therapy in the US Veterans Health Administration (VHA) database. Methods: Newly diagnosed mRCC pts treated with 1L TKIs followed by 2L therapy were identified between OCT2013-MAR2018 within the VHA database (1L start date = index date). Eligible pts were required to have continuous enrollment for ≥6 months post-2L therapy initiation unless the pt died. A Kaplan-Meier (KM)-derived median time to 2L therapy initiation was used as the cut-off to categorize pts into early (≤median) and delayed ( > median) progression cohorts. KM analysis and Cox proportional hazards models were used to compare and assess the impact of predictive factors on clinical outcomes including overall survival (OS), time to 2L discontinuation (index date to 2L discontinuation or death), and time to 3L treatment initiation (index date to 3L start or death) among pts in the early vs delayed progression cohorts. Results: Among 289 mRCC pts, the mean age was 67.4 years and the median time to 2L initiation was 6.1 months. Pt characteristics were similar between the early (n = 145) and delayed (n = 144) progression cohorts. During follow-up, the delayed progression cohort had better clinical outcomes than the early progression cohort did (Table below). Conclusions: Early progression is associated with worse clinical outcomes, confirming the need to delay disease progression among mRCC pts with effective 1L treatment strategies. Results indicate the need for use of more efficacious therapies, e.g. immuno-oncology-based combinations, in 1L that can delay disease progression and have potential to reduce disease burden. [Table: see text]

e17017 Background: Anti-PD-1/PD-L1 agents are US FDA-approved for patients with advanced or metastatic UC, but limited information exists on real world irAEs among this patient population. We examined the rates and time to onset of select irAEs in UC patients receiving PD-L1s vs PD-1s in the real world. Methods: This observational study included US commercial and Medicare Advantage health plan members from Optum Research Database with UC and treated with a PD-1 or PD-L1 agent between 01-Sep-14 and 30-Apr-19. Baseline characteristics were assessed ≤ 6-months prior to the first claim for anti-PD-1/PD-L1. 21 irAEs were chosen a priori based on the ASCO clinical guideline on irAE management, clinical input, frequency, and cost of treatment. Patients were followed for newly occurring irAEs, based on claims ICD codes, during the PD-1/PD-L1 therapy and up to 180 days after if no new treatment, study period end, death, or disenrollment. Kaplan-Meier method was utilized to calculate time to onset of irAEs. Results: The study included 240 patients receiving PD-L1s and 317 receiving PD-1s. Baseline demographics were similar (Table). The most common irAEs were 1) thyroid disorders, 2) impaired ventricular function with heart failure and vasculitis, 3) rash, and 4) nephritis. UC patients receiving PD-L1s had a lower rate of irAEs vs PD-1s, mainly driven by lower rates of hematologic and endocrine toxicities (Table). UC patients receiving a PD-L1 also had longer time to irAE onset (p-value = 0.05). Conclusions: UC patients receiving PD-L1s had a lower incidence rate of irAEs and longer time to irAE onset than patients on PD-1s. Findings suggest patients receiving PD-1s may require more intense monitoring for irAEs than patients taking PD-L1s. [Table: see text]

643 Background: In 2019, there was an estimated 73,820 new cases of kidney cancers in the US. The tx landscape for aRCC is changing rapidly. Recently approved txs for 1L aRCC include new targeted agents and immuno-oncology (IO) therapies. We examine outcomes for pts who completed 1L tx. Methods: Real-world data were drawn from the RCC Disease Specific Programme; a cross-sectional survey administered to US oncologists, nephrologists and urologists. Physicians completed pt record forms (PRFs) for up to the next 8 consulting aRCC pts receiving drug tx, from February - September 2019, plus additional optional PRFs for pts receiving/who had received either 1L tx of nivolumab/ipilimumab combination or cabozantinib, where these pts were available. Results: Physicians (n=82) provided data on 687 pts; 230 had progressed from 1L tx and were on 2L tx at time of data collection. Of those receiving 2L tx, 61% male; mean age was 66.4 years (SD=11.0); 43% stage IV at diagnosis. At 1L, 72% (n=165) had received tyrosine kinase inhibitor (TKI) monotherapy; 16% (n=37) IO+IO, 3% (n=7) TKI+IO and 9% (n=20) other regimens. Mean 1L duration was 10.3 months (SD=9.4) and mean time to 2L initiation was 13.7 months (SD=21.1). 1L treatment responses were: 6% complete response, 21% partial response, 16% stable disease, and the remainder relapsed/progressed (44%) or unknown response (13%). Most common 2L regimens were TKI (37%) or IO (34%) monotherapy. 47% of 1L TKI monotherapy pts received 2L IO monotherapy. 86% of 1L IO+IO pts received 2L TKI monotherapy. Conclusions: Some pts with aRCC progress to 2L; many experience poor clinical outcomes with 1L txs, highlighting high unmet need in 1L for more efficacious txs. Optimal tx strategy (and sequencing) continues to evolve. Approval of IO+TKI therapies, approved during the fieldwork period, has broadened the therapeutic landscape for 1L aRCC. Whilst the proportion of 1L pts receiving IO+TKI therapies is still low, the adoption of these in 1L is likely to transform the management of aRCC. Further research is needed to determine the optimum tx sequence in these pts with high unmet need.

Aim: To explore factors associated with pembrolizumab (PEMBRO) versus ipilimumab + nivolumab (IPI+NIVO) selection in advanced melanoma. Materials & methods: Total of 12 academic and satellite clinics contributed to this study. Descriptive and logistic regression analyses were conducted to explore associations between clinical characteristics and treatment choice. Results: Total of 400 patients were included: 200 PEMBRO and 200 IPI+NIVO. Patients were significantly more likely to receive PEMBRO versus IPI+NIVO if they had poorer Eastern Cooperative Oncology Group score, 2–4 versus 0–1 (odds ratio [OR]: 6.6; 95% CI: 3.0–14.7), if they were PD-L1 positive (OR: 4.5; 95% CI: 1.9–10.4) or had BRAF wild-type tumor (OR: 2.2; 95% CI: 1.4–3.6). Conclusion: Patient factors are significantly associated with treatment selection in advanced melanoma. Outcomes comparisons should take this into consideration.

Background Personalised tx is key in aRCC. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model determines prognosis of aRCC patients treated with systemic tx, helping guide treatment choice. This study examined real-world tx patterns and outcomes of 1L aRCC patients with differing IMDC status in the US. Methods Real-world data were drawn from the RCC Disease Specific ProgrammeTM; a cross-sectional study administered to oncologists, nephrologists and urologists in the US. Physicians completed patient record forms (PRFs) for up to the next 8 consulting RCC patients receiving active drug tx, from February - September 2019, plus additional optional PRFs for patients receiving/who had received either 1L nivolumab/ipilimumab combination tx or cabozantinib tx, where these patients were available. Study variables included patient demographics, background clinical information and tx patterns. Results Physicians (n = 82) provided data on 687 patients. 445 patients were receiving 1L tx at time of data abstraction. Of those receiving 1L tx, mean age was 64.2 years, and 69% of patients were male. 34% (n = 151) did not have a physician-assessed IMDC prognostic risk score, and 5% (n = 23) reported unknown. Of the 61% (n = 271) that had a physician-assessed IMDC prognostic risk score, 15% had a low risk, 63% had an intermediate risk and 21% had a high risk. In the intermediate and high risk group, tyrosine kinase inhibitor (TKI) monotherapy was the most common 1L therapy (45%, n = 103), followed by IO-IO combination (29%, n = 66). Conclusion ASCO and NCCN guidelines recommend IO-IO combination in patients with an intermediate or high IMDC risk. However, at the time of data collection, more patients meeting these criteria received TKI monotherapy than IO-IO combination; moreover, almost a third of 1L tx aRCC patients were not even assessed. Newly introduced IO-TKI combination tx, approved during the fieldwork period, could enable clinicians to offer patients personalised tx, irrespective of risk profile. Legal entity responsible for the study Pfizer Inc. Funding Pfizer Inc. (part of an alliance between Pfizer Inc. and Merck KGaA, Darmstadt, Germany). Disclosure G. Zanotti: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer. R. Kim: Full / Part-time employment: Pfizer; Shareholder / Stockholder / Stock options: Exelixis. S.P. Krulewicz: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer. J.P. Hall: Full / Part-time employment: Adelphi Real World. A. Leith: Full / Part-time employment: Adelphi Real World. A. Bailey: Full / Part-time employment: Adelphi Real World. F. Liu: Full / Part-time employment: EMD Serono, Inc. M. Kearney: Full / Part-time employment: Merck KGaA, Darmstadt, Germany; Shareholder / Stockholder / Stock options: Novartis Pharma; Shareholder / Stockholder / Stock options: UCB Pharma; Shareholder / Stockholder / Stock options: SPRL.

Given the ever-increasing burden of end-stage renal disease (ESRD) in a global milieu of limited financial and health resources, interested parties continue to search for ways to optimize dialysis access. Government and payer initiatives to increase access to renal replacement therapies (RRTs), particularly peritoneal dialysis (PD) and hemodialysis (HD), may have meaningful impacts from clinical and health-economic perspectives; and despite similar clinical and humanistic outcomes between the two dialysis modalities, PD may be the more convenient and resource-conscious option. This review assessed country-specific PD-First/Favored policies and their associated background, implementation, and outcomes. It was found that barriers to policy-implementation are broadly associated with government policy, economics, provider or healthcare professional education, modality-related factors, and patient-related factors. Notably, the success of a given country's PD-Favored policy was inversely associated with the extent of HD infrastructure. It is hoped that this review will provide a foundation across countries to share lessons learned during the development and implementation of PD-First/Favored policies.

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology.

Background Understanding the perceptions of patients and oncology nurses about the relative importance of benefits and risks associated with newer treatments of advanced melanoma can help to inform clinical decision-making. Objectives The aims of this study were to quantify and compare the views of patients and oncology nurses regarding the importance of attributes of treatments of advanced melanoma. Methods A discrete choice experiment (DCE) was conducted in US-based oncology nurses and patients diagnosed with advanced melanoma. Patients and nurses were enlisted through online panels. In a series of scenarios, respondents had to choose between 2 hypothetical treatments, each with 7 attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (DoT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to estimate preference weights. Results A total of 200 patients with advanced melanoma and 150 oncology nurses participated. The relative importance estimates of attributes by patients and nurses, respectively, were as follows: OS, 33% and 28%; AEs, 29% and 26%; ORR, 25% and 27%; PFS, 12% and 15%; DS, 2% and 3%; DoT, 0% and 0%; and MoA, 0% and 0%. Conclusion Both patients and oncology nurses valued OS, ORR, and AEs as the most important treatment attributes for advanced melanoma, followed by PFS, whereas DS, DoT, and MoA were given less value in their treatment decisions. Implications for practice Oncology nurses and patients have similar views on important treatment considerations for advanced melanoma, which can help build trust in shared decision-making.

Background With limited healthcare resources available, cost-effective provision of dialysis to patients with end-stage renal disease (ESRD) is important. Objectives To assess the cost-effectiveness of varying levels of peritoneal dialysis (PD) use versus current practice among incident ESRD patients requiring dialysis. Methods A Markov model was developed to investigate the cost-effectiveness of increasing uptake of PD to 39 and 50 % versus current practice of 22 % PD from a UK National Health Service perspective for the year of 2013–2014. A scenario with 5 % PD was also considered. Sensitivity analyses were performed. Results Five- and 10-year discounted total costs and quality-adjusted life years (QALYs) per patient for the current scenario (22 % PD) were £96,307 and 2.104, and £133,339 and 3.301, respectively. Use of PD in 39 % of patients resulted in 5- and 10-year total per-patient cost savings of £3,180 and £4,102 versus current usage alongside total per-patient QALY increases of 0.017 and 0.020. Use of PD in 50 % of patients resulted in 5- and 10-year per-patient cost savings of £5,238 and £6,758 versus current usage alongside per-patient QALY increases of 0.029 and 0.033. Thus, increasing use of PD was associated with marginally better outcomes and lower costs. Cost savings were driven by lower treatment costs and reduced transport requirements for PD versus haemodialysis. Reducing PD use was associated with higher costs and a small reduction in QALYs. Conclusions These findings suggest increasing PD use among incident dialysis patients would be cost-effective, associated with reduced costs and potential modest improvements in quality of life. Electronic supplementary material The online version of this article (doi:10.1007/s40258-014-0108-7) contains supplementary material, which is available to authorized users.

Recently, the effectiveness of novel immune checkpoint inhibitors and BRAF-directed therapies has been demonstrated in advanced melanoma trial populations. Limited research, however, has evaluated the impact of these therapies in a real-world setting. The aim of this study was to evaluate treatment patterns and clinical outcomes among advanced melanoma patients treated with modern therapies within community oncology clinics. Adult patients with advanced melanoma who initiated treatment within the US Oncology Network between 1/1/14 and 12/31/16 were included. Data were sourced from electronic healthcare records. Patients were followed through 12/31/17. Descriptive analyses were performed to assess patient and treatment characteristics and Kaplan-Meier methods were used for time-to-event outcomes. In total, 484 patients met eligibility criteria (32.0% with brain metastasis, 12.6% with Eastern Cooperative Oncology Group performance status ≥2). In the first-line (1L) setting during the study period, 37.0% received anti-PD1 monotherapies, 26.4% ipilimumab monotherapy, 19.8% BRAF/MEK combination therapy, 6.4% BRAF or MEK monotherapy, 4.1% ipilimumab/nivolumab combination therapy and 6.2% other regimens. Differences in baseline demographic and clinical characteristics were observed across treatment groups. For the overall study population, the median (95% confidence interval) estimates for overall survival, time to next treatment and progression-free survival were 20.7 (16.0, 26.8), 5.8 (5.3, 6.5), and 4.9 (4.2, 5.7) months, respectively. The results of this study provide real-world insight into advanced melanoma treatment trends and clinical outcomes, including high utilization of immunotherapies and BRAF/MEK combination therapy. Future research can explore underlying differences in patient subpopulations and the sequence of therapies across lines of therapy.

Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal

9532 Background: Both pembrolizumab (PEMBRO) and combination ipilimumab + nivolumab (IPI+NIVO) are FDA-approved immunotherapies for advanced melanoma (AM). These two treatment regimens have different toxicity profiles which may impact health care resource utilization (HCRU). Our aim was to compare real-world risk of hospitalization and emergency department (ED) visits within 12 months of starting the two treatment regimens. Methods: A retrospective cohort study was conducted in patients ≥18 years old with AM initiating PEMBRO or IPI+NIVO between Jan 1, 2016 – Dec 30, 2017. Patients were identified from 12 US academic medical centers and affiliated satellite clinics. Data were abstracted through chart review. All-cause hospitalizations or ED visits and the rates per patient per month (PPPM) through 12 months of follow-up were calculated. Utilization was compared between PEMRBO and IPI+NIVO using multivariate logistic regression analysis. Results: 400 patients were included, 200 each PEMBRO and IPI+NIVO with mean (SD) follow-up time of 10 (3) and 10 (4) months, respectively. The PEMBRO cohort had poorer Eastern Cooperative Group (ECOG) performance status at treatment start, 71% ECOG 0 or 1 vs 88% (p < .001); more diabetes, 21% vs 13% (p = .045); a trend towards more heart disease, 18% vs 12% (p = .067); were more likely to be PD-L1 expression positive, 77% vs 63% (p = .011); and less likely to harbor a BRAF mutation, 35% vs 50% (p = .003). The proportion with at least one hospitalization through 12 months was 17% PEMBRO vs 24% IPI+NIVO. Less than 2% of patients had more than one admission and none had more than two, regardless of cohort. Unadjusted mean (SD) PPPM hospitalizations were .016 (.037) for PEMBRO and .020 (.038) for IPI+NIVO. The adjusted odds ratio for any hospitalization with PEMBRO was 0.55 (95% CI .31, .97; p = .039) vs. IPI+NIVO. ED visits occurred in 18% vs 21% in PEMBRO and IPI+NIVO respectively, with no difference in covariate-adjusted analysis (p = .147). Conclusions: Patients receiving PEMBRO had a significantly lower probability of hospitalization and similar probability of ER visits compared with IPI+NIVO in the real world through 12 months.

e21004 Background: Pembrolizumab (PEMBRO) and combination ipilimumab + nivolumab (IPI+NIVO) are FDA-approved immunotherapies for advanced melanoma (AM). HRQoL was better maintained with PEMBRO vs IPI in KEYNOTE-006. CheckMate-067 reported no clinically meaningful HRQoL differences with IPI+NIVO vs IPI. As randomized trial data are lacking, we compared HRQoL outcomes in AM between PEMBRO and IPI+NIVO in real-world clinical settings. Methods: A prospective, observational study was conducted with sponsor blinded to sites, and sites blinded to sponsor; nine oncologists from 9 US academic centers and affiliated satellite clinics enrolled AM patients (pts) age ≥18 years initiating first-line PEMBRO or IPI+NIVO between June 2017 – March 2018. The European Organization for the Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C30) and EQ-5D-5L were administered at baseline and weeks 6, 12, 18, and 24 following therapy. Least squared (LS) mean changes in HRQoL scores from baseline were compared using mixed-effects models for repeated measures, adjusting for baseline covariates. Results: A total of 225 PEMBRO and 187 IPI+NIVO pts were enrolled, with > 95% questionnaire completion rates through week 24. At baseline, PEMBRO pts were more likely > age 65 (49% vs 37%, p = .011), stage IV disease (92% vs 85%; p = .002), and higher comorbidity index (1.0 vs 0.6; p < .001) compared with IPI+NIVO pts. Adjusted EORTC global health status/quality of life (GHS) LS mean changes from baseline showed greater improvement with PEMBRO vs. IPI+NIVO at 12, 18 and 24 weeks. At week 24, PEMBRO pts achieved a 3.3-point improvement (95% CI = 0.8, 5.7) and IPI+NIVO pts had no significant change (1.0, 95% CI = -1.6, 3.5), with a LS mean difference of 2.3 points (p = .037; 95% CI = 0.14, 4.51). At week 24, the EQ-5D visual analogue scale increased 1.0 (95% CI, -1.2, 3.2) for PEMBRO vs IPI+NIVO which decreased 0.9 (95% CI = -3.2, 1.3), with a statistically significant LS mean difference of 2.0 (95% CI = 0.4, 3.9; p = .045). Conclusions: Results from 2 measures suggest HRQoL was maintained vs. baseline in both PEMBRO and IPI+NIVO pts, with a significant between-group difference favoring PEMBRO in GHS over 24 weeks.

137 Background: Immunotherapies (I/Os) have demonstrated improved overall survival vs. chemotherapy for patients (pts) with metastatic melanoma (MM). However, little is known about the comparative health care resource utilization (HCRU) among different I/Os. This study examined the real world HCRU across different I/Os: PD-1 inhibitors (pembrolizumab (PEM) or nivolumab (NIVO), PD-1), CTLA-4 inhibitor (ipilimumab, IPI), and combination of I/Os (IPI+NIVO). Methods: A retrospective observational study was conducted using a large US payer claims data. Adults with ≥2 claims for MM and ≥1 claim for metastasis were identified between 1/1/2012 and 6/30/2017 and followed through 9/30/2017. All pts had pharmacy and medical claims and ≥6 months pre-index enrollment. HCRU was calculated per pt per month (PPPM) and by percentages across PD-1, IPI, IPI+NIVO from Index date until the first occurrence of: change in regimen, end of continuous enrollment, or end of study period. Adjusted odds ratios (OR) for HCRU were estimated using logistic regressions to control for baseline patient characteristics. Results: On average, pts in the PD-1 cohort (n = 255) were older than those in IPI (n = 555) and IPI+NIVO (n = 88) cohorts (mean 68 vs 63 and 63, both p < 0.05) and had less brain metastasis (22% vs 34% and 31%, p < 0.05 and p = 0.11, respectively). During 1L therapy, fewer PD-1 pts had any hospitalization (HOSP, 25.9% vs 39.8% and 45.5%, both p < 0.05), fewer HOSPs PPPM (mean 0.06 vs 0.10 and 0.14, both p < 0.05), and fewer ER visits PPPM (mean 0.09 vs 0.13 and 0.18, both p < 0.05) compared to IPI and IPI+NIVO, respectively. Any 30-day re-HOSP and ER visits were numerically lower with PD-1 compared with IPI and IPI+NIVO, but not statistically significant (13.7% vs 19.1% and 18.2%; 40.0% vs 47.0% and 50.0% respectively). Adjusting for baseline characteristics, pts treated with IPI and IPI+NIVO were more likely to have a HOSP than PD-1s (OR = 2.10, 95% CI, 1.44-3.07; and 2.35; 95% CI, 1.32-4.12, both p < 0.01). Conclusions: Pts treated with IPI or IPI+NIVO had significantly increased odds of being hospitalized and higher HOSP and ER visits PPPM compared to PD-1s. Further studies are warranted to confirm these findings.

IntroductionHealth Technology Assessment (HTA) and regulatory decisions involve value judgements. As patient groups, industry, and regulatory agencies conduct more preference studies to quantify these judgements, a better understanding of the methods and practices is needed. Currently, there is no systematic mapping of the use of preference data in Europe. This study aimed to identify (i) the use of quantitative preference data by all relevant HTA bodies and regulatory authorities of the European Union (EU) member states, and (ii) key standards and guidelines.MethodsThis study used a mixed method approach based on a systematic literature review, survey and subsequent interviews with decision makers and experts.ResultsA total of 62 survey responses were received. Many respondents reported that their agencies were responsible for supporting more than one type of decision, with 69.0 percent supporting approval decisions, 64.3 percent supporting reimbursement decisions, 61.9 percent supporting pricing decisions, and 64.2 percent supporting guideline development. Respondents reported that their agencies supported these decisions in multiple ways: 78.6 percent by assessing health technologies; 54.8 percent by appraising health technologies; 45.2 percent by compiling an HTA report; 7.1 percent by conducting primary research; 9.5 percent by conducting secondary research. More than 40 percent (42.9 percent) of agencies had the final say on one of the decisions of interest – approval, reimbursement, or pricing. Of the 31 countries studied, 71 percent (n = 22) used quantitative preference data in their reimbursement and pricing decisions. Of those, 86 percent (n = 19) used general population preferences to inform the estimation of quality-adjusted life years (QALY) as part of cost utility analysis.ConclusionsMuch of this use of preference data can be understood within the standard framework of economic analysis adopted by many HTA agencies; either in in the form of: standard ways to estimate QALYs; ways to broaden the impacts of technologies captured in the QALY; or ways to weigh health gain with other decision-making criteria, such as disease severity or innovativeness.

ObjectivesFew studies have examined hospitalization costs for unplanned initiation of peritoneal dialysis (PD). We used data from a health care facility in Mexico to examine first hospitalization costs associated with the unplanned initiation of PD.MethodsDescriptive analyses focusing on initial hospitalization costs during the unplanned initiation of PD were conducted. In addition, multivariate regression models examined the association of costs with requiring urgent hemodialysis (HD) at the time of starting PD, and the association of driving distance with requiring urgent HD.ResultsOf 195 patients hospitalized in 2010 for PD catheter placement, 51 patients met criteria for unplanned PD initiation and 25 of them required urgent HD prior to PD initiation. Ninety-two percent of the patients received 90% or greater government subsidy of hospital costs. Average inpatient costs for the first hospitalization related to the unplanned initiation of PD were 64,174 Mexican Pesos (MXN) (US $4,657). Costs were 78,683 MXN ($5,710) per patient for those requiring urgent HD and 50,225 MXN ($3,645) for those who did not, a difference (P

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.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/mBase 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.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.

Parenteral nutrition (PN) is critical in neonatal and pediatric care for patients unable to tolerate enteral feeding. This study assessed the total costs of compounding PN therapy for neonates, infants and children.Face-to-face and telephone interviews were conducted in 12 hospitals across four European countries (Belgium, France, Germany and UK) to collect information on resources utilized to compound PN, including nutrients, staff time, equipment cost and supplies. A bottom-up cost model was constructed to assess total costs of PN therapy by assigning monetary values to the resource utilization using published list prices and interview data.A total of 49,922 PN bags per year were used to treat 4295 neonatal and pediatric patients among these hospitals. The daily total costs of one compounded PN bag for neonates in the 12 hospitals across the four countries equalled euro 55.16 (Belgium euro 53.26, France euro 46.23, Germany euro 64.05, UK Ł 37.43/\[euro]42.86). Overall, nutrients accounted for 25% of total costs, supplies 18%, wages 54% and equipment 3%. Average costs per bag for infants2 year were euro 84.52 (euro 74.65 in Belgium, euro 83.84 in France, euro 92.70 in Germany and Ł 52.63/euro 60.26 in the UK), and for children 2-18 years euro 118.02 (euro 93.85 in Belgium, euro 121.35 in France, euro 124.54 in Germany and Ł 69.49/euro 79.56 in the UK), of which 63% is attributable to nutrients and 28% to wages.The data indicated that PN costs differ among countries and a major proportion was due to staff time (Ł 1=euro 1.144959).

The implementation of Medicare Part D on January 1, 2006 provided a voluntary outpatient prescription drug benefit to 43 million Medicare beneficiaries for the first time since Medicare's inception (Doherty 2004). Following the implementation of Part D, Medicare's portion of national prescription drug spending increased from 2 percent (2005) to 18 percent (2006) (Kaiser Family Foundation 2008). Around 50–60 percent of Medicare beneficiaries without prior prescription drug coverage had Part D drug coverage in 2006 (Levy and Weir 2009). The estimated federal cost of Part D from 2007 through 2016 is U.S.$768 billion dollars (Kaiser Family Foundation 2006). Studies have found that Part D increased Medicare beneficiaries' prescription utilization and decreased their out-of-pocket costs (Lichtenberg and Sun 2007; Simoni-Wastila et al. 2008; Yin et al. 2008;). However, it is less clear whether the program has led to reductions, or offsets, in nonprescription utilization of health care services. Khan, Kaestner, and Lin (2008) used data from the 1992–2000 Medicare Current Beneficiary Survey and found that prescription drug insurance did not appear to reduce beneficiary's hospitalizations. In contrast, Hsu et al. (2006) analyzed Medicare Part C claims data from Kaiser Permanente–Northern California and concluded that increases in medication coverage resulted in reduced hospitalizations and lower health care expenditures. Similarly, Zhang et al. (2009) analyzed claims data from a Medicare Advantage plan for a Pennsylvania insurer 2 years before and 2 years after the implementation of Part D and found that the increased spending on prescription drugs was offset by lower nondrug medical spending among groups with limited or no previous drug coverage. We sought to study the overall policy impact of Part D on non-low-income Medicare beneficiaries using detailed health care utilization and expenditure data from a large, nationally representative sample of Medicare beneficiaries. This study hypothesized that Part D eligibility would be associated with an increase in Medicare beneficiaries' medication utilization and a reduction in their out-of-pocket costs for prescription drugs, emergency department use, and hospitalization rates (Gellad et al. 2006; Tjia and Schwartz 2006;) as well as improvement in Medicare beneficiaries' overall health measured by preference-based health utility.

Background: Bloodstream infections (BSI) occur in up to 350 000 inpatient admissions each year in the US, with BSI rates among patients receiving parenteral nutrition (PN) varying from 1.3% to 39%. BSI-attributable costs were estimated to approximate &dollar;US12 000 per episode in 2000. While previous studies have compared the cost of different PN preparation methods, this analysis evaluates both the direct costs of PN and the treatment costs for BSI associated with different PN delivery methods to determine whether compounded or manufactured pre-mixed PN has lower overall costs. Objective: The purpose of this study was to compare costs in the US associated with compounded PN versus pre-mixed multi-chamber bag (MCB) PN based on underlying infection risk. Methods: Using claims information from the Premier Perspective™ database, multivariate logistic regression was used to estimate the risk of infection. A total of 44 358 hospitalized patients aged ≥18 years who received PN between 1 January 2005 and 31 December 2007 were included in the analyses. A total of 3256 patients received MCB PN and 41 102 received compounded PN. The PN-associated costs and length of stay were analysed using multivariate ordinary least squares regression models constructed to measure the impact of infectious events on total hospital costs after controlling for baseline and clinical patient characteristics. Results: There were 7.3 additional hospital days attributable to BSI. After adjustment for baseline variables, the probability of developing a BSI was 30% higher in patients receiving compounded PN than in those receiving MCB PN (16.1% vs 11.3%; odds ratio - 1.56; 95% CI 1.37, 1.79; p < 0.0001), demonstrating 2172 potentially avoidable infections. The observed daily mean PN acquisition cost for patients receiving MCB PN was &dollar;US164 (including all additives and fees) compared with &dollar;US239 for patients receiving compounded PN (all differences p < 0.001). With a mean cost attributable to BSI of &dollar;US16 141, the total per-patient savings (including avoided BSI and PN costs) was &dollar;US1545. Conclusion: In this analysis of real-world PN use, MCB PN is associated with lower costs than compounded PN with regards to both PN acquisition and potential avoidance of BSI. Our base case indicates that &dollar;US1545 per PN patient may be saved; even if as few as 50% of PN patients are candidates for standardized pre-mix formulations, a potential savings of &dollar;US773 per patient may be realized.

Supplemental Digital Content is available in the text, Background: Treatments for advanced melanoma are associated with different adverse events (AEs), which may be costly to manage. This study aimed to evaluate direct costs associated with managing treatment-related AEs for advanced melanoma through a systematic literature review. Methods: Systematic searches were conducted of the PubMed, Embase, Cochrane, BIOSIS, and EconLit medical literature databases to identify studies providing estimates of direct costs and health care resource utilization for the management of AEs of melanoma treatments, published between January 1, 2007, and February 23, 2017. Gray literature searches also were conducted. Studies reporting direct costs for patients with advanced melanoma that were published in English between 2007 and 2017 were eligible. Studies were systematically screened in 2 phases by 2 independent reviewers. Study design details and data on direct costs by country were extracted. Results: Seven studies evaluating the cost of AEs in patients with advanced melanoma were included; most estimated the costs for grade 3 or 4 events. In a United States study, monthly AE costs constituted 36.9% of overall health care costs for dacarbazine, 30.3% for paclitaxel, 9.2% for temozolomide, 6.4% for vemurafenib, and 4.0% for ipilimumab. A multicountry study found the greatest cost per event to be for grade 3 or 4 AEs associated with ipilimumab, including colitis (A$1471 [Australia]–€3313 [France]) and diarrhea (£2836 [United Kingdom]), and chemotherapy (neutropenia/leukopenia in Germany [€1744] and Italy [€804]). Across studies, cost drivers for the most expensive AEs to manage were requiring hospitalization or use of expensive outpatient medications and/or procedures (eg, erythropoietin and blood transfusions for anemia). Some currently available therapies were not available during the research period, and their associated AEs are not reflected. Results may not be comparable across countries. For some studies, resource-use estimates reflect practice patterns from a limited number of centers, limiting generalizability. Conclusion: Costs for managing each type of AE associated with the treatment of advanced melanoma are substantial. Effective treatments with improved safety profiles may help reduce total AE management costs.