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Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50%

Open AccessPublished:October 16, 2021DOI:https://doi.org/10.1016/j.jval.2021.08.009

      Highlights

      • In 2020, the cost of cancer care in the United States has been estimated to be ∼$173 billion. Non-small cell lung cancer (NSCLC) is the fifth costliest tumor type in the United States (∼$13.6 billion in 2016). Advances in cancer immunotherapy have provided significant benefits in terms of increased survival for patients relative to chemotherapy in NSCLC; nevertheless, the relative clinical benefits, including reduced toxicity compared with chemotherapeutic agents, must also be measured in terms of economic impact.
      • Cemiplimab is a programmed death-1 inhibitor approved for the treatment of patients with advanced cutaneous squamous cell carcinoma and has demonstrated antitumor activity in other advanced solid tumors. In the phase III EMPOWER-Lung 1 trial, first-line cemiplimab monotherapy demonstrated significantly improved overall survival and progression-free survival versus platinum doublet chemotherapy in patients with advanced NSCLC with programmed death-ligand 1 expression in ≥50% of tumor cells.
      • This analysis demonstrates that cemiplimab is a cost-effective treatment option from a US commercial payer perspective compared with pembrolizumab or chemotherapy for the first-line treatment of patients with advanced NSCLC and ≥50% programmed death-ligand 1 expression.

      Abstract

      Objectives

      This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

      Methods

      A 30-year “partitioned survival” model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties.

      Results

      Cemiplimab was associated with increased time in the “preprogression” (13.08 vs 7.90 and 6.08 months) and “postprogression” (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI −0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy.

      Conclusions

      Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

      Keywords

      Introduction

      Lung malignancies have been the leading cause of cancer-related mortality over the last decade, exceeding the combined rates for the other most prevalent malignancies, including colon, breast, and prostate cancers.
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      Systemic treatment of advanced NSCLC with PD-1/PD-L1 inhibitors is administered as either monotherapy or in combination with chemotherapy or another immunotherapy. Nevertheless, physicians seek additional treatment options that will avoid the toxicity associated with chemotherapy, especially in patients with high PD-L1 expression levels.
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      Based on the benefits of monotherapy, this cost-effectiveness analysis (CEA) focused on monotherapy options for NSCLC. Pembrolizumab (anti–PD-1) is approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of adult patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (TPS ≥1%) as determined by a FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
      FDA expands pembrolizumab indication for first-line treatment of NSCLC (TPS ≥1%). Food and Drug Administration.
      Atezolizumab (anti–PD-L1) as monotherapy is also approved by the US FDA for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area), as determined by a FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
      FDA approves atezolizumab for first-line treatment of metastatic NSCLC with high PD-L1 expression. Food and Drug Administration.
      Atezolizumab data were determined to not be relevant to this analysis based on the different assay used to measure PD-L1 expression.
      Cemiplimab is a highly potent, human, hinge-stabilized, IgG4 monoclonal antibody directed against PD-1. In 2017, cemiplimab was approved for the treatment of metastatic cutaneous squamous cell carcinoma and locally advanced cutaneous squamous cell carcinoma not amenable to curative surgery/radiotherapy
      • Migden M.R.
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      • et al.
      PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma.
      ,
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      • Chang A.L.S.
      • et al.
      Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.
      and has demonstrated antitumor activity in other advanced solid tumors.
      • Papadopoulos K.P.
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      • Lockhart A.C.
      • et al.
      First-in-human study of cemiplimab alone or in combination with radiotherapy and/or low-dose cyclophosphamide in patients with advanced malignancies.
      Recent results from EMPOWER-Lung 1, a phase III trial (NCT03088540), demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) with first-line cemiplimab monotherapy versus platinum doublet chemotherapy in patients with advanced NSCLC (stage IIIB/IIIC or stage IV) and PD-L1 expression ≥50% (using the PD-L1 immunohistochemistry [IHC] 22C3 pharmDx assay [Agilent Technologies]).
      • Sezer A.
      • Kilickap S.
      • Gümüş M.
      • et al.
      Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial.
      Consequently, in 2021, cemiplimab was approved in the United States for the first-line treatment of patients with advanced NSCLC negative for actionable molecular markers and PD-L1 expression ≥50%.
      LIBTAYO® [cemiplimab-rwlc] injection full US prescribing information. Regeneron Pharmaceuticals Inc.
      The cost of cancer care in the United States has been estimated to be ∼$173 billion in 2020.
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      Projections of the cost of cancer care in the United States: 2010-2020 [published correction appears in J Natl Cancer Inst. 2011;103(8):699].
      NSCLC is the fifth costliest tumor type in the United States (approximately $13.6 billion in 2016).
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      Understanding total cost of care in advanced non-small cell lung cancer pre- and postapproval of immuno-oncology therapies.
      ,
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      Advances in cancer immunotherapy continue to emerge, with every new approved treatment providing significant benefits in terms of increased survival of patients relative to chemotherapy in NSCLC. Nevertheless, the relative clinical benefits between these immunotherapies, including reduced toxicity compared with chemotherapeutic agents, must also be measured in terms of economic impact.
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      A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors.
      Such evidence is crucial to inform health technology appraisals and support payer and clinical decision making. Hence, cost-effectiveness data against relevant alternative treatment options are required for cemiplimab to be considered an economically valuable first-line monotherapy.
      This study evaluates the cost-effectiveness for cemiplimab versus pembrolizumab, another PD-1 inhibitor monotherapy considered to be the current standard of care (SOC) in the United States for advanced NSCLC with PD-L1 ≥50%
      • Smit E.F.
      • de Langen A.J.
      Pembrolizumab for all PD-L1-positive NSCLC.
      ,
      ESMO Asia 2015 news: pembrolizumab ‘new standard-of-care’ in advanced NSCLC after platinum-based chemotherapy. European Society for Medical Oncology.
      and chemotherapy, the historical SOC.

      Methods

      The CEA was conducted from a US commercial payer perspective. The target population was patients with advanced NSCLC tumors expressing PD-L1 levels ≥50% based on TPS. A 30-year time horizon was considered sufficient to capture the remaining lifetime of these patients given that the average age of the target patient population was 63.1 years. The expected mean OS for these patients is 5 years with cemiplimab. Mortality and morbidity outcomes were represented by quality-adjusted life-years (QALYs).

       Model Structure

      The CEA model was based on a “partitioned survival” structure, which is the most common model structure for CEA of advanced or metastatic oncologic therapies.
      • Verma V.
      • Sprave T.
      • Haque W.
      • et al.
      A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors.
      • Woods B.
      • Sideris E.
      • Palmer S.
      • et al.
      NICE DSU technical support document 19: partitioned survival analysis for decision modelling in health care: a critical review. The National Institute for Health and Care Excellence.
      This approach aligns with the endpoints observed in the cemiplimab clinical trial (PFS and OS) and allows the time dependency in the risk of events over time to be captured, with survival modeled as a function of time since model entry.
      • Woods B.
      • Sideris E.
      • Palmer S.
      • et al.
      NICE DSU technical support document 19: partitioned survival analysis for decision modelling in health care: a critical review. The National Institute for Health and Care Excellence.
      The area under the PFS curve is used to model the number of patients in the “preprogression” health state over time. The area above the OS curve is used to model the number of patients in the “death” health state, and the area between the OS and PFS curves is used to model the number of patients in the “postprogression” health state (see Appendix Fig. 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009).
      All patients entered the model in the “preprogression” health state, where they received cemiplimab or a comparator treatment. Over time, patients transitioned either to the “death” health state or to the “postprogression” health state where they received subsequent treatment before moving to the “death” health state.

       Model Inputs

      A summary of key base case parameter values and rationale from the US perspective is presented in Table 1.
      Table 1Summary of key base case and scenario analysis parameter values and rationales.
      ParameterRationale
      Base case
      Treatment comparatorsCemiplimab versus pembrolizumab and platinum doublet chemotherapyComparison of current and historical SOC
      Time horizon30 yearsAssumed equal to lifetime
      Discount rate (costs and outcomes)3.0%US: Academy of Managed Care Pharmacy guidelines
      PerspectiveUS healthcare payerAligns with purpose of project
      Cycle length1 monthAllows for alignment across potential treatment periodicities
      Half-cycle correctionYesReduces bias
      ExtrapolationChemotherapy reference: Extrapolation of hazard trend

      Hazard ratios for pembrolizumab and cemiplimab: time-varying hazard ratios kept constant beyond 36 months
      Assumes treatment effects are applied for full extrapolation
      Cemiplimab dosingA flat dose of 350 mg administered intravenously infusion on day 1 of every 3 weeksIn line with the trial
      Cemiplimab clinical dataEnrolled population from EMPOWER-Lung 1Best available evidence
      Adverse event probabilitiesUnadjusted estimates from clinical trialsBest available evidence
      Adverse event costsTop-down costsUS specific costs
      Utility preprogressionHealth state utility values from Chouaid et al
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      2013
      US: US Tariff
      Utility postprogressionHealth state utility values from Chouaid et al
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      2013
      Preprogression maximum treatment capAssumed treat until progression for cemiplimab

      Pembrolizumab has a max. treatment duration of 2 years

      Chemotherapy assumed treatment duration of 6 cycles. Patients who receive cisplatin plus pemetrexed will receive pemetrexed maintenance treatment until progression
      Aligns with cemiplimab clinical trial design US FDA label of respective products and previous NICE submissions for advanced NSCLC
      Postprogression subsequent therapiesDocetaxelBased on SOC for second-line NSCLC
      FDA indicates Food and Drug Administration; NICE, National Institute for Health and Care Excellence; NSCLC, non-small cell lung cancer; SOC, standard of care.

       Clinical Evidence

      The clinical activity of cemiplimab was based on individual patient level data from the PD-L1 ≥50% population of EMPOWER-Lung 1.
      • Sezer A.
      • Kilickap S.
      • Gümüş M.
      • et al.
      Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial.
      This trial enrolled patients aged ≥18 years with histologically or cytologically confirmed stage IIIB/IIIC, who were not candidates for definitive chemoradiotherapy, or with untreated stage IV (patients who had received adjuvant or neoadjuvant chemotherapy were eligible if they met the protocol criteria) squamous or nonsquamous NSCLC with PD-L1 expressed in ≥50% of tumor cells. PD-L1 expression was determined at a central laboratory via PD-L1 IHC 22C3 pharmDx assay.
      To inform the clinical inputs for the model, a systematic literature review following health technology assessment standards (International Society for Pharmacoeconomics and Outcomes Research, National Institute for Health and Care Excellence [NICE], and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines)
      Good practices for outcomes research. ISPOR.
      The guidelines manual (Process and methods [PMG6]). National Institute for Health and Care Excellence.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
      was conducted in October 2019 to identify randomized controlled trials of relevant first-line treatment options in advanced NSCLC with high (TPS ≥50%) PD-L1 expression. A total of 3 relevant phase III randomized controlled trials of pembrolizumab monotherapy versus investigator’s choice of chemotherapy were identified in the systematic literature review: KEYNOTE-024,
      • Reck M.
      • Rodríguez-Abreu D.
      • Robinson A.G.
      • et al.
      Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater.
      KEYNOTE-042,
      • Mok T.S.K.
      • Wu Y.L.
      • Kudaba I.
      • et al.
      Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.
      and the KEYNOTE-042 China study.
      • Wu Y.
      • Zhang L.
      • Fan Y.
      • et al.
      MA11. 02 KEYNOTE-042 China study: first-line pembrolizumab vs chemotherapy in Chinese patients with advanced NSCLC with PD-L1 TPS≥ 1%.
      Network meta-analyses (NMAs) were then performed to assess the comparative efficacy of cemiplimab, pembrolizumab, and chemotherapy. The KEYNOTE-042 China Extension Study was excluded from the NMA due to patient overlap with the KEYNOTE-042 trial and differences in study location. In the EMPOWER-Lung 1 and KEYNOTE trials, PD-L1 expression was quantified using the 22C3 pharmDx assay, whereas in the IMpower110 trial,
      • Herbst R.S.
      • Giaccone G.
      • de Marinis F.
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      Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC.
      the primary method used to quantify PD-L1 expression to determine eligibility was the VENTANA SP142 assay. The comparability and interchangeability of the 22C3 and SP142 assays have been evaluated in the literature with reports of the SP142 assay being associated with lower sensitivity and specificity relative to the 22C3 assay in determining high PD-L1 expression.
      • Tsao M.S.
      • Kerr K.M.
      • Kockx M.
      • et al.
      PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint Phase 2 project.
      • Rimm D.L.
      • Han G.
      • Taube J.M.
      • et al.
      A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer.
      • Hirsch F.R.
      • McElhinny A.
      • Stanforth D.
      • et al.
      PD-L1 immunohistochemistry assays for lung cancer: results from Phase 1 of the blueprint PD-L1 IHC assay comparison project.
      • Torlakovic E.
      • Lim H.J.
      • Adam J.
      • et al.
      “Interchangeability” of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy.
      • Zajac M.
      • Scott M.
      • Ratcliffe M.
      • et al.
      Concordance among four commercially available, validated programmed cell death ligand-1 assays in urothelial carcinoma.
      • Xu H.
      • Lin G.
      • Huang C.
      • et al.
      Assessment of concordance between 22C3 and SP142 immunohistochemistry assays regarding PD-L1 expression in non-small cell lung cancer.
      • Koomen B.M.
      • Badrising S.K.
      • van den Heuvel M.M.
      • Willems S.M.
      Comparability of PD-L1 immunohistochemistry assays for non-small-cell lung cancer: a systematic review.
      • Buttner R.
      • Gosney J.R.
      • Skov B.G.
      • et al.
      Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer.
      • Velcheti V.
      • Patwardhan P.D.
      • Liu F.X.
      • Chen X.
      • Cao X.
      • Burke T.
      Real-world PD-L1 testing and distribution of PD-L1 tumor expression by immunohistochemistry assay type among patients with metastatic non-small cell lung cancer in the United States.
      The lowest sensitivity and specificity of the SP142 assay are corroborated by the PD-L1 IHC Assay Comparison Project,
      • Tsao M.S.
      • Kerr K.M.
      • Kockx M.
      • et al.
      PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint Phase 2 project.
      ,
      • Hirsch F.R.
      • McElhinny A.
      • Stanforth D.
      • et al.
      PD-L1 immunohistochemistry assays for lung cancer: results from Phase 1 of the blueprint PD-L1 IHC assay comparison project.
      which indicated that patients with PD-L1 expression of approximately 50% to 60% as assessed by the SP142 assay had a PD-L1 expression of approximately 80% to 98% with the 22C3 or 29-8 assay. Given the incomparability of the 2 assays, the IMpower110 study was excluded from the base case NMA.
      Therefore, 3 trials were included in the NMA: EMPOWER-Lung 1, KEYNOTE-024,
      • Reck M.
      • Rodríguez-Abreu D.
      • Robinson A.G.
      • et al.
      Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater.
      and KEYNOTE-042.
      • Mok T.S.K.
      • Wu Y.L.
      • Kudaba I.
      • et al.
      Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.
      All 3 trials used the 22C3 pharmDx assay to measure PD-L1 expression levels. The target population for the NMA aligned with the CEA and only included patients with PD-L1 ≥50%. KEYNOTE-042 included patients with PD-L1 ≥1%, and therefore, only subgroup-level data for patients with PD-L1 ≥50% were included in the NMA.

       Extrapolation of Survival in the Economic Model

      To estimate health outcomes over a lifetime time horizon, PFS and OS were extrapolated until all patients had progressed or died. Extrapolations were based on best practice guidelines by the NICE Decision Support Unit.
      • Woods B.
      • Sideris E.
      • Palmer S.
      • et al.
      NICE DSU technical support document 19: partitioned survival analysis for decision modelling in health care: a critical review. The National Institute for Health and Care Excellence.
      OS was capped using age-adjusted mortality rates for the US general population (Fig. 1A ).
      National vital statistics system, mortality data. Centers for Disease Control and Prevention.
      PFS was capped using age-adjusted PFS rates for the US general population (Fig. 1B). These curves described the proportion of patients in each of 3 health states of the cost-effectiveness model (“preprogression,” “postprogression,” and “death”) for each intervention. The proportion of patients in the “pre- and postprogression” health states were multiplied with corresponding utility estimates (discounted over time) and summated over time to obtain treatment-specific estimates of expected QALYs. Similarly, expected costs by treatment were calculated given treatment received and resource use associated with “pre- and postprogression” health states distributions (again discounted over time).
      Figure thumbnail gr1
      Figure 1Modeled (A) overall survival and (B) progression-free survival.
      CI indicates confidence interval.
      The chemotherapy arm of the EMPOWER-Lung 1 trial was used as the reference treatment in the economic model, because this was the common comparator in the NMA network. The baseline hazards for chemotherapy were estimated by fitting parametric curves to the patient level data from the EMPOWER-Lung 1 trial and extrapolating over the lifetime model horizon. Competing survival functions were considered for each endpoint: exponential, Weibull, Gompertz, log-normal, and log-logistic and a range of second order fractional polynomial models. The fit of the models to the observed data was assessed using the Akaike information criteria; the tails of the PFS and OS functions were inspected visually to assess whether the extrapolations were plausible from clinical perspectives (avoiding any implausible survival plateaus) based on clinical input and validation with published economic models in first-line NSCLC. One related previous health technology appraisal submission conducted by NICE in 2018 (TA531) was identified for pembrolizumab in PD-L1-positive NSCLC.
      Pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer. National Institute for Health and Care Excellence.
      In TA531, the evidence review group noted that the 5-year survival for chemotherapy patients in this population should be at least 5%, in line with data from the UK National Lung Cancer Audit.
      National Lung Cancer Audit Annual report 2016 (for the Audit Period 2015). Royal College of Physicians.
      Surveillance, Epidemiology, and End Results survival statistics for patients with widely metastatic NSCLC in the United States also demonstrate a 5-year survival rate of 4.5%.
      Lung and bronchus cancer
      SEER survival rates by time since diagnosis, 2000-2016. Surveillance Epidemiology and End Results Program.
      To this end, an exponential distribution was selected to model the chemotherapy arm of the EMPOWER-Lung 1 trial because it provided both a good visual fit to the data and estimated survival of 6% at year 5, which is in line with NICE and Surveillance, Epidemiology, and End Results estimates for this population (see Appendix Table 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009).
      Lung and bronchus cancer
      SEER survival rates by time since diagnosis, 2000-2016. Surveillance Epidemiology and End Results Program.
      ,
      Single technology appraisal 531: pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer. National Institute for Health and Care Excellence.
      It was also compatible with the second-best fitting fractional polynomial used to model the time-varying hazard ratios (HRs) for cemiplimab and pembrolizumab. A Weibull model was used to estimate PFS for chemotherapy, because it provided a good fit to the observed data (Akaike information criterion 1066.9) and was compatible with the best fitting fractional polynomial model distribution for modeling the HRs (see Appendix Table 2 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009). There was less uncertainty in the long-term extrapolations for PFS, because 70% of events occurred during the observed period and the estimated probability of PFS at 12 months was 7.1%.
      Fractional polynomial models fit to time-varying HRs estimated from the NMA were used to estimate OS and PFS for cemiplimab and pembrolizumab. The models were selected according to goodness of fit, compatibility with the model used for the reference curve, and clinical plausibility of the long-term extrapolation. The HRs were kept constant beyond 36 months because there were no observed data available beyond this period to inform the NMA. Given that the fractional polynomial extrapolation estimates an HR that is monotonically decreasing, this assumption was deemed to be conservative. The second-best fitting fractional polynomial (P1 = 0, P2 = 1) was used to estimate the OS HRs because this provided good compatibility with the parametric curve selected to model the baseline hazards. The best fitting fractional polynomial was used to model the PFS HRs for cemiplimab and pembrolizumab (P1 = 0, P2 = 1).

       Treatment Duration

      For cemiplimab, time to treatment discontinuation was assumed in the model to be equal to time spent in the “preprogression” health state. For pembrolizumab, patients were assumed to receive treatment while in the “PFS” health state up to a maximum of 2 years in line with the product license. Although the stopping rule was used to restrict costs associated with pembrolizumab beyond 2 years, the clinical benefit associated with the treatment was assumed to remain unchanged following this stopping rule. This assumption is conservative. To assess the sensitivity around this assumption and given that pembrolizumab clinical efficacy data in first-line NSCLC beyond 5 years are currently unavailable, an additional scenario analysis was explored whereby the pembrolizumab treatment effect was maintained for up to 10 years, after which point a treatment waning effect is applied, and the hazard rate is set equal to that of chemotherapy for the rest of the time horizon.
      Patients in the chemotherapy arm were assumed to receive treatment while in the “PFS” health state up to a maximum of 6 cycles. Patients who received the pemetrexed plus cisplatin combination received maintenance treatment until progression. After disease progression, all patients are assumed to receive treatment with docetaxel in the second line for a mean treatment duration of 6 months.

       Adverse Events, Utilities, Cost, and Resource Use

      All model inputs regarding clinical activity, utilities, drug acquisition cost, drug administration cost, treatment duration, adverse events (AEs), and disease management costs are presented in Table 2.
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      • Nafees B.
      • Stafford M.
      • Gavriel S.
      • Bhalla S.
      • Watkins J.
      Health state utilities for non small cell lung cancer.
      • Tabberer M.
      • Stamuli E.
      • Walker M.
      • Summerhayes M.
      • Lees M.
      PCN74 utilities associated with non-small cell lung cancer (NSCLC): a community study.
      FDA approves LIBTAYO® (cemiplimab-rwlc) as first and only treatment for advanced cutaneous squamous cell carcinoma. Regeneron Pharmaceuticals Inc.
      Physician fee schedule search. Centers for Medicare and Medicaid Services.
      Healthcare cost and utilization project (HCUP). Agency for Healthcare Research and Quality.
      Consumer price index. United States Bureau of Labor Statistics.
      • Chastek B.
      • Harley C.
      • Kallich J.
      • Newcomer L.
      • Paoli C.J.
      • Teitelbaum A.H.
      Health care costs for patients with cancer at the end of life.
      Health state utility values for PFS and progressive disease were 0.71 and 0.67, respectively, based on Chouaid et al
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      (2013) (Table 2; Appendix Table 3). In terms of safety inputs, only grade 3 or 4 AEs reported in at least 5% of the patients in the clinical trials were considered in the model, because these AEs were expected to incur higher costs and have a greater impact on health-related quality of life (see Appendix Table 4 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009). Therefore, utility decrements associated with treatment-related AEs were applied in the first cycle of the model and were assumed to only occur once for 1 month (Table 2) (Nafees et al
      • Nafees B.
      • Stafford M.
      • Gavriel S.
      • Bhalla S.
      • Watkins J.
      Health state utilities for non small cell lung cancer.
      [2008]; Tabberer et al
      • Tabberer M.
      • Stamuli E.
      • Walker M.
      • Summerhayes M.
      • Lees M.
      PCN74 utilities associated with non-small cell lung cancer (NSCLC): a community study.
      [2006]). Drug acquisition and monitoring costs were included for preprogression treatment and postprogression treatment (see Appendix Table 5 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009). The analysis accounted for costs associated with AE management (see Appendix Table 4 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009), disease management (see Appendix Tables 6 and 7 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009), and terminal care (Table 2). All costs were adjusted for inflation to 2019 US dollar using the medical care component of the Consumer Price Index.
      Table 2Source data for cost-effectiveness model inputs.
      ParameterModel inputReference
      PFS and OS parameters
       Parametric model fit to PFS for chemotherapy arm of EMPOWER-Lung 1 trialWeibullNetwork meta-analysis
       Fractional polynomial model fit to time-varying hazard ratios for pembrolizumab and cemiplimabP1 = 0, P2 = –1
       Parametric model fit to OS for chemotherapy arm of EMPOWER-Lung 1 trialExponential
       Fractional polynomial fit to time-varying hazard ratios for pembrolizumab and cemiplimabP1 = 0, P2 = 1
      Utilities
       Preprogression utility0.71Chouaid et al
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      2013
       Postprogression utility0.67
      AEs
       Rash–0.030Nafees et al
      • Nafees B.
      • Stafford M.
      • Gavriel S.
      • Bhalla S.
      • Watkins J.
      Health state utilities for non small cell lung cancer.
      2008; Tabberer et al
      • Tabberer M.
      • Stamuli E.
      • Walker M.
      • Summerhayes M.
      • Lees M.
      PCN74 utilities associated with non-small cell lung cancer (NSCLC): a community study.
      2006
       Alopecia0.000
       Aspartate aminotransferase increased0.000
       Alanine aminotransferase increased0.000
       White blood cell count decreased0.000
       Platelet count decreased0.000
       Neutrophil count decreased0.000
       Diarrhea–0.050
       Nausea–0.050
       Hypomagnesemia0.000
       Fatigue–0.070
       Asthenia0.000
       Anemia0.000
       Neutropenia–0.090
       Thrombocytopenia0.000
       Leukopenia0.000
       Stomatitis–0.140
      Drug acquisition cost, per month
       Cemiplimab, preprogression$13 181US list price for cemiplimab
      FDA approves LIBTAYO® (cemiplimab-rwlc) as first and only treatment for advanced cutaneous squamous cell carcinoma. Regeneron Pharmaceuticals Inc.
       Pembrolizumab, preprogression$14 296ProspectoRx, September 2020
       Pemetrexed, preprogression$10 714.92
       Cisplatin, preprogression$78.43
       Gemcitabine, preprogression$172.42
       Paclitaxel, preprogression$118.91
       Docetaxel, postprogression treatment$393.24
      Drug administration cost, per model cycle
       Cemiplimab, preprogression$135.69CMS HCPCS coding
      Physician fee schedule search. Centers for Medicare and Medicaid Services.
       Pembrolizumab, preprogression$135.69
       Chemotherapy, preprogression$135.69
       Postprogression (subsequent treatment)$135.69
      Treatment duration
       CemiplimabUntil progressionCemiplimab summary of product characteristics
       Pembrolizumab2-year stopPembrolizumab summary of product characteristics
       Chemotherapy: Paclitaxel + cisplatin, gemcitabine + cisplatin6 cyclesChemotherapy summary of product characteristics
       Chemotherapy: Pemetrexed + cisplatin6 cycles followed by maintenance treatment with pemetrexed until progressionChemotherapy summary of product characteristics
      AEs cost, first cycle only
       Rash$6577.70HCUP national inpatient sample (2017)
      Healthcare cost and utilization project (HCUP). Agency for Healthcare Research and Quality.
      using ICD-10-CM codes per AE, adjusted for inflation to 2019 USD using medical care component of CPI
      Consumer price index. United States Bureau of Labor Statistics.
       Alopecia$0.00
       Aspartate aminotransferase increased$0.00
       Alanine aminotransferase increased$0.00
       White blood cell count decreased$0.00
       Platelet count decreased$13 105.32
       Neutrophil count decreased$13 656.39
       Diarrhea$7853.11
       Nausea$7660.29
       Hypomagnesemia$7112.50
       Fatigue$8099.62
       Asthenia$8099.62
       Anemia$7940.76
       Neutropenia$13 656.39
       Thrombocytopenia$13 105.32
       Leukopenia$13 105.32
       Stomatitis$17 144.72
      Disease management costs
       PFS, per model cycle$446Chastek et al
      • Chastek B.
      • Harley C.
      • Kallich J.
      • Newcomer L.
      • Paoli C.J.
      • Teitelbaum A.H.
      Health care costs for patients with cancer at the end of life.
      2012 inflated to 2019 USD
       Postprogression survival, per model cycle$744
       Terminal care cost$31 823.72
      Note. The full list of ICD-10-CM codes per AE is available in Appendix Table 4 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009.
      AE indicates adverse event; CMS, Centers for Medicare and Medicaid Services; CPI, consumer price index; HCPCS, Healthcare Common Procedure Coding System; HCUP, Healthcare Cost and Utilization Project; ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; OS, overall survival; PFS, progression-free survival; USD, US dollar.

       Cost-Effectiveness Analyses

      Deterministic analysis was performed for the base case, with life-years (LYs), QALYs, costs, and incremental cost-effectiveness ratio (ICER) based on point estimates. A discount of 3% was applied to health outcomes and costs.
      • Sullivan S.D.
      • Lyles A.
      • Luce B.
      • Grigar J.
      AMCP Guidance for submission of clinical and economic evaluation data to support formulary listing in U.S. health plans and pharmacy benefits management organizations.
      The sensitivity of the ICER to key parameters of the model was assessed by 1-way sensitivity analysis and summarized as a tornado diagram (Fig. 2A, vs pembrolizumab; Fig. 2B, vs chemotherapy). Parameters were varied sequentially using their lower and upper bounds based on 95% confidence (or credible) intervals (CrI), either as reported or, where unavailable, based on the standard error assuming 10% of point estimate.
      Figure thumbnail gr2
      Figure 2Tornado plot of base case one-way sensitivity analysis of the ICER versus (A) pembrolizumab and (B) chemotherapy.
      ICER indicates incremental cost-effectiveness ratio; OS, overall survival; PD, progressive disease; PF, progression-free; PFS, progression-free survival; QALY, quality-adjusted life-year.
      Probabilistic sensitivity analysis was performed to evaluate parameter uncertainty; parameter values were sampled from (posterior) distributions for clinical activity (normal distribution), safety (β distribution), utilities (β distribution), and costs (γ distribution) for each iteration of the model. The model was evaluated by averaging output values from 1000 iterations. Base case probabilistic sensitivity analysis is depicted as a scatter plot (Fig. 3A), cost-effectiveness acceptability curves of cemiplimab versus pembrolizumab (Fig. 3B), and cemiplimab versus chemotherapy (Fig. 3C). These results were used to derive the probability of being cost-effective at different willingness-to-pay (WTP) thresholds ($0-$200 000 US dollar) presented as cost-effectiveness acceptability curves.
      Figure thumbnail gr3
      Figure 3Base case probabilistic sensitivity analysis: (A) scatter plot, (B) cost-effectiveness acceptability curves of cemiplimab versus pembrolizumab (1000 iterations), and (C) cost-effectiveness acceptability curves of cemiplimab versus chemotherapy (1000 iterations).
      QALY indicates quality-adjusted life-year.
      Additional scenario analyses were conducted to assess the sensitivity of the base case on key assumptions (Table 3).
      Table 3Cost-effectiveness analysis results; base case and scenario analyses.
      Base case (disaggregated results)
      CemiplimabPembrolizumabChemotherapy
      PFS time (in months)13.087.906.08
      Postprogression survival time (in months)47.3029.4914.78
      Life-years5.033.121.74
      Discounted life-years4.282.821.65
      Discounted QALYs; preprogression0.750.460.36
      Discounted QALYs; progressive disease2.171.450.77
      Discounted QALYs2.911.911.13
      Discounted drug acquisition and admin cost; preprogression$168 887$110 299$23 292
      Discounted drug acquisition and admin cost; progressive disease$2902$3125$3309
      Discounted total drug acquisition and admin cost$171 789$113 423$26 601
      Discounted disease management cost; preprogression$5627$3463$2684
      Discounted disease management cost; progressive disease$28 872$19 382$10 288
      Discounted disease management cost; terminal care$27 709$29 170$30 268
      Discounted total disease management costs$62 207$52 016$43 240
      Discounted adverse event costs$237$641$5265
      Discounted total direct cost$234 233$166 081$75 106
      Incremental discounted costs-$68 153$159 127
      95% CI low$17 144$112 434
      95% CI high$133 946$220 377
      Incremental discounted QALYs0.9991.784
      95% CI low−0.2660.607
      95% CI high2.4403.20
      Incremental cost per QALY$68 254$89 219
      Probabilistic value$70 312$88 832
      Scenario analyses
      Base case inputScenarioICER vs pembrolizumabICER vs chemotherapy
      Base case resultsN/A$68 254$89 219
      Base case PFS: Weibull used to model EMPOWER-Lung 1 chemotherapyAlternative PFS: Fractional polynomial used to model EMPOWER-Lung 1 chemotherapy$137 819$131 393
      Base case OS: Exponential used to model EMPOWER-Lung 1 chemotherapyAlternative OS: Weibull used to model EMPOWER-Lung 1 chemotherapy$84 741$110 715
      Time-varying HRs modeled from NMA and then kept constant beyond 36 monthsTreatment waning scenario for pembrolizumab: treatment effect stopped at 5 years$58 178-
      Pembrolizumab query treatment costs applied until 24-month stopping rulePembrolizumab costs applied until progression (no stopping rule)$65 919-
      Health state utility values from Chouaid et al
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      2013
      Health state utility values from KEYNOTE-024 (used in UK NICE submission)$66 562$87 586
      Health state utility values from Chouaid et al
      • Chouaid C.
      • Agulnik J.
      • Goker E.
      • et al.
      Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.
      2013
      Health state utility values from EMPOWER-Lung-1$59 342$77 654
      CI indicates confidence interval; HR, hazard ratio; ICER, incremental cost-effectiveness ratio; N/A, not applicable; NICE, National Institute for Health and Care Excellence; NMA, network meta-analyses; OS, overall survival; PFS, progression-free survival; QALY, quality-adjusted life-year.

      Results

       NMA

      NMAs were performed using a fixed effects fractional polynomial model for OS and PFS. The resulting time-varying HRs for cemiplimab versus pembrolizumab or chemotherapy are presented in Appendix Table 8 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2021.08.009. Cemiplimab was consistently associated with a statistically meaningful improvement in OS and PFS versus chemotherapy. The OS HR was 0.69 (95% CrI 0.48-0.99) at 3 months and 0.29 (95% CrI 0.14-0.60) at 30 months, and the PFS HR was 0.78 (95% CrI 0.61-1.00) at 3 months and 0.07 (95% CrI 0.04-0.14) at 30 months. Cemiplimab was associated with an improvement in PFS versus pembrolizumab (3 months, HR 0.82; 95% CrI 0.60-1.12; 30 months, HR 0.32; 95% CrI 0.15-0.68), with statistically meaningful differences observed from 6 months to 30 months. Cemiplimab was also associated with an improvement in OS versus pembrolizumab (3 months, HR 0.83; 95% CrI 0.54-1.29; 30 months, HR 0.61; 95% CrI 0.28-1.34), although results were not statistically meaningful.

       Base Case CEA

      In the base case (Table 3), cemiplimab was associated with increased time in both the “preprogression” (13.08 vs 7.90 and 6.08 months) and “postprogression” (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Cemiplimab was also associated with increased LYs (4.28 LYs) compared with pembrolizumab (2.82 LYs) and chemotherapy (1.65 LYs).
      After applying utility weights to the LYs gained per treatment arm, cemiplimab-treated patients accrued 2.91 versus 1.91 and 1.13 QALYs accrued by pembrolizumab- and chemotherapy-treated patients, respectively. This resulted in an incremental discounted QALY gain for cemiplimab versus pembrolizumab and chemotherapy of 1.00 and 1.78, respectively.
      Consistent with the increased time spent by cemiplimab-treated patients in a progression-free state, total discounted costs for cemiplimab ($234 233) were higher than for pembrolizumab ($166 081) and for chemotherapy ($75 106) (Table 3). Cemiplimab was associated with an incremental cost per QALY gained of $68 254 and $89 219 versus pembrolizumab and chemotherapy, respectively (Table 3). In addition, the incremental cost per QALY gained for pembrolizumab versus chemotherapy in this model was $115 885.

       Probabilistic Sensitivity Analysis

      The probabilistic ICERs were $70 312 per QALY versus pembrolizumab and $88 312 per QALY versus chemotherapy, corresponding to results from the base case deterministic CEA. Simulations from the probabilistic sensitivity analysis indicated that treatment with cemiplimab was likely to be more effective and more costly than treatment with either pembrolizumab or chemotherapy, with 90% of the iterations for cemiplimab versus pembrolizumab falling in the northeast quadrant of the cost-effectiveness plane. Treatment with cemiplimab was likely to be more effective and more costly than treatment with chemotherapy, with 100% of the iterations falling in the northeast quadrant of the cost-effectiveness plane. The cost-effectiveness acceptability curve provided a 67% to 78% probability of cemiplimab being cost-effective versus pembrolizumab and a probability of 73% to 92% of being cost-effective versus chemotherapy, at a WTP threshold of $100 000 to $150 000 (Fig. 3).

       Scenario Analyses

      Scenario analyses indicated that the model was most sensitive to changes to the assumptions used to model OS and PFS (Table 3). Even when alternative scenarios were considered as in Table 3, the results are still within the WTP threshold of $100 000 to $150 000. The base case results were conservative in assuming a lifetime effect for pembrolizumab following the 24-month stopping rule; in the scenario where a 10-year waning effect was used, the cost-effectiveness of cemiplimab versus pembrolizumab was even more apparent than in the base case ($65 639).

      Discussion

      Our findings suggest that cemiplimab is a cost-effective monotherapy option for patients with advanced NSCLC with PD-L1 ≥50%. The ICERs were driven by favorable OS and PFS estimates for cemiplimab compared with both pembrolizumab and chemotherapy.
      In the base case, cemiplimab provided an additional (discounted) 1.47 LYs and 1.00 QALYs compared with pembrolizumab and 2.63 LYs and 1.78 QALYs compared with chemotherapy. The increased PFS associated with cemiplimab (and hence increased time spent in the progression-free state) was associated with higher total discounted costs for cemiplimab than for pembrolizumab. The base case ICERs, $68 254 per QALY versus pembrolizumab and $89 219 per QALY versus chemotherapy, were below the $100 000 to $150 000 WTP threshold recommended by the Institute of Clinical and Economic Review,
      Review
      Final value assessment framework for 2017-2019. Institute for Clinical and Economic.
      suggesting that cemiplimab is a cost-effective intervention in this patient population. The model was most sensitive to OS and PFS assumptions, because the model assumed that all patients in the cemiplimab arm were treated until progression. The PFS curve selected in this scenario had a strong plateau with approximately 9.5% of patients still progression-free and receiving treatment at year 5. All scenarios provided results that fell within the $150 000 ICER threshold for cost-effectiveness.
      The methods used in this analysis are based on best practice guidelines
      • Ramsey S.D.
      • Willke R.J.
      • Glick H.
      • et al.
      Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.
      and a modeling approach that is consistent with established methods for patients with advanced-stage malignancy.
      • Woods B.
      • Sideris E.
      • Palmer S.
      • et al.
      NICE DSU technical support document 19: partitioned survival analysis for decision modelling in health care: a critical review. The National Institute for Health and Care Excellence.
      ,
      • Goeree R.
      • Villeneuve J.
      • Goeree J.
      • Penrod J.R.
      • Orsini L.
      • Tahami Monfared A.A.
      Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.
      A key strength of our analysis was the homogenous biomarker patient population on which the clinical inputs to the model were based.
      Review
      ICER releases evidence report on treatments for non-small cell lung cancer. Institute for Clinical and Economic.
      ,
      NCCN clinical practice guidelines in oncology: non-small cell lung cancer. NCCN.
      The cost-effectiveness of pembrolizumab versus chemotherapy in this analysis is comparable with other published assessments of first-line anti–PD-1 immunotherapy versus SOC for advanced NSCLC with PD-L1 ≥50%. Two such studies in NSCLC were conducted from the US healthcare payer perspective: within a study that applied the “partitioned survival” modeling approach with a cycle length of 1 week and a base case time horizon of 20 years, gains of 1.31 LYs/1.05 QALYs and incremental cost per QALY of $97 621 were observed.
      • Huang M.
      • Lou Y.
      • Pellissier J.
      • et al.
      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.
      In another analysis based on a separate Bayesian Markov model of disease with full lifetime horizon, results obtained were 1.80 LYs/1.06 QALYs and $49 000 incremental cost per QALY.
      • Georgieva M.
      • da Silveira Nogueira Lima J.P.
      • Aguiar Jr., P.
      • de Lima Lopes Jr., G.
      • Haaland B.
      Cost-effectiveness of pembrolizumab as first-line therapy for advanced non-small cell lung cancer.
      Uncertainty in the OS and PFS estimates represents the key limitation of this analysis and is also seen in other oncology cost-effectiveness analyses.
      • Huang M.
      • Lou Y.
      • Pellissier J.
      • et al.
      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.
      ,
      Single Technology Appraisal 990: pembrolizumab for untreated PD-L1 positive metastatic non-small-cell lung cancer. National Institute for Health and Care Excellence.
      ,
      Single Technology Appraisal 1559: nivolumab for previously treated squamous non-small-cell lung cancer. National Institute for Health and Care Excellence.
      Parametric distributions have been used to extrapolate these endpoints over the lifetime time horizon of the model. There is inherent uncertainty in the use of this methodology, and the PFS and OS estimates for these treatment arms have been shown in 1-way sensitivity analyses to be key drivers for the results. The level of uncertainty has been quantified by running scenario analyses to assess how changes to these assumptions affect the results. On the other hand, PFS, OS, and lifetime costs also tend to be interrelated, a nuance that is not well displayed in 1-way sensitivity analyses. That is, even if future research were to show that the predicted increases in PFS and OS associated with cemiplimab versus pembrolizumab were smaller than anticipated, the present study findings would likely be unchanged. This is due to the 8% lower list price of cemiplimab compared with pembrolizumab. Even if cemiplimab had only equivalent efficacy to pembrolizumab with identical OS and PFS curves, cemiplimab would remain the cost-effective option by virtue of its lower list price.
      Although best practices were followed to account for between-study differences, there remains uncertainty whether any unknown or unmeasured prognostic factors are missing from the models that may influence the outcomes of interest. In addition, head-to-head comparisons for cemiplimab versus pembrolizumab are currently unavailable; hence, caution should be taken in drawing conclusions about relative efficacy versus serving as required inputs for modeling purposes for payers following best practices.
      The financial burden of advanced NSCLC, especially with increased stage of disease, is considerable in terms of direct cost to the healthcare systems and indirect costs to society, patients, and caregivers
      • Wood R.
      • Taylor-Stokes G.
      Cost burden associated with advanced non-small cell lung cancer in Europe and influence of disease stage.
      ,
      • Skinner K.E.
      • Fernandes A.W.
      • Walker M.S.
      • Pavilack M.
      • VanderWalde A.
      Healthcare costs in patients with advanced non-small cell lung cancer and disease progression during targeted therapy: a real-world observational study.
      ; as such, the need for newer, more cost-effective and safer treatments for NSCLC that slow or prevent disease progression or induce disease regression is paramount. The limited clinical utility of chemotherapy in patients with advanced NSCLC given newer treatment options is well established, particularly in patients who may be unable to tolerate the side effects of the most potent regimens.
      Review
      Treatment options for advanced non-small cell lung cancer: effectiveness, value and value-based price benchmarks. Institute for Clinical and Economic.
      PD-1 inhibitors have offered a new level of therapeutic armamentarium for the target patient population with increased expression of PD-L1 and, given the level of benefits, have been proclaimed as the new SOC.
      • Korytowsky B.
      • Radtchenko J.
      • Nwokeji E.D.
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      • Kish J.K.
      • Feinberg B.A.
      Understanding total cost of care in advanced non-small cell lung cancer pre- and postapproval of immuno-oncology therapies.
      Despite inherent limitations in survival extrapolations, these findings suggest that compared with pembrolizumab and chemotherapy, cemiplimab monotherapy is a cost-effective first-line treatment option for advanced NSCLC with PD-L1 ≥50%.

      Article and Author Information

      Author Contributions: Concept or design: Kuznik, Smare, Chen, Atsou, Xu, Guyot, and Konidaris
      Acquisition of data: Smare, Venkatachalam, Keeping, Wilson, Chan, and Glowienka
      Analysis and interpretation of data: Kuznik, Smare, Chen, Venkatachalam, Keeping, Atsou, Xu, Wilson, Guyot, Chan, Glowienka, and Konidaris
      Drafting of the manuscript: Kuznik, Smare, Chen, Venkatachalam, Keeping, Atsou, Xu, Wilson, Guyot, Chan, Glowienka, and Konidaris
      Critical revision of the paper for important intellectual content: Kuznik, Smare, Chen, Venkatachalam, Keeping, Atsou, Xu, Wilson, Guyot, Chan, Glowienka, and Konidaris
      Statistical Analysis: Smare, Chan
      Obtaining Funding: Kuznik, Chen, Xu, Konidaris
      Administrative, technical, or logistical support: Chen, Xu, Konidaris
      Supervision: Chen, Konidaris
      Conflict of Interest Disclosures: Drs Kuznik and Chen are employees and shareholders of Regeneron Pharmaceuticals, Inc. Drs Smare, Keeping, Wilson, Chan, Glowienka, and Venkatachalam are employees of Precision HEOR and reported received funding from Regeneron Pharmaceuticals, Inc., and Sanofi during the conduct of this study. Dr Xu is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Drs Atsou, Guyot, and Konidaris are employees and shareholders of Sanofi. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.
      Funding/Support: This study was supported by Regeneron Pharmaceuticals, Inc . and Sanofi .
      Role of the Funder/Sponsor: The funder provided input on the design and conduct of the analysis; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

      Acknowledgment

      Writing support was provided by Gauri Saal, MA, Economics of Prime (Knutsford, UK); this was funded by Regeneron Pharmaceuticals, Inc. and Sanofi according to Good Publication Practice guidelines (https://www.ismpp.org/gpp3).

      Supplemental Material

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