{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:46:32Z","timestamp":1775011592214,"version":"3.50.1"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","award":["2019JJ50864"],"award-info":[{"award-number":["2019JJ50864"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"crossref","award":["B2019156"],"award-info":[{"award-number":["B2019156"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC). Taken into account the clinical benefits of pembrolizumab and its high cost, this study aimed to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the US payer perspective.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examine the robustness of our model.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Adding pembrolizumab to standard first-line EP resulted in the better effectiveness than EP chemotherapy alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio (ICER) of $334,373\/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerted no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide range of willingness to pay were modest.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compared with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary to improve its cost-effectiveness.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0258605","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T18:36:36Z","timestamp":1637001396000},"page":"e0258605","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line therapy for extensive-stage small-cell lung cancer"],"prefix":"10.1371","volume":"16","author":[{"given":"Qiao","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongqing","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidan","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liubao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6050-4137","authenticated-orcid":true,"given":"Xiaohui","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"pone.0258605.ref001","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pharmthera.2017.06.002","article-title":"Treatment advances in small cell lung cancer (SCLC)","volume":"180","author":"SN Waqar","year":"2017","journal-title":"Pharmacol Ther"},{"issue":"1","key":"pone.0258605.ref002","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41598-017-01571-0","article-title":"Survival changes in patients with small cell lung cancer and disparities between different sexes, socioeconomic statuses and ages","volume":"7","author":"S Wang","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0258605.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"RL Siegel","year":"2019","journal-title":"CA Cancer J Clin"},{"issue":"10","key":"pone.0258605.ref004","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/ng.2396","article-title":"Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer","volume":"44","author":"M Peifer","year":"2012","journal-title":"Nat Genet"},{"issue":"6","key":"pone.0258605.ref005","doi-asserted-by":"crossref","first-page":"vi99","DOI":"10.1093\/annonc\/mdt178","article-title":"Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","author":"M Fr\u00fch","year":"2013","journal-title":"Ann. Oncol"},{"issue":"34","key":"pone.0258605.ref006","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1200\/JCO.2015.63.7918","article-title":"Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline","volume":"33","author":"CM Rudin","year":"2015","journal-title":"J. Clin. Oncol"},{"issue":"7","key":"pone.0258605.ref007","first-page":"731","article-title":"The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV","volume":"24","author":"H Akamatsu","year":"2019","journal-title":"J. Clin. Oncol"},{"issue":"1","key":"pone.0258605.ref008","doi-asserted-by":"crossref","first-page":"69","DOI":"10.21037\/tlcr.2018.01.16","article-title":"Current standards for clinical management of small cell lung cancer","volume":"7","author":"AF Farago","year":"2018","journal-title":"Transl Lung Cancer Res"},{"key":"pone.0258605.ref009","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.lungcan.2019.12.015","article-title":"A systematic review of survival following anti-cancer treatment for small cell lung cancer","volume":"141","author":"GS Jones","year":"2020","journal-title":"Lung Cancer"},{"issue":"23","key":"pone.0258605.ref010","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa1809064","article-title":"First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer","volume":"379","author":"L Horn","year":"2018","journal-title":"N Engl J Med"},{"issue":"10212","key":"pone.0258605.ref011","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(19)32222-6","article-title":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial","volume":"394","author":"L Paz-Ares","year":"2019","journal-title":"Lancet"},{"issue":"21","key":"pone.0258605.ref012","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1200\/JCO.20.00793","article-title":"Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study","volume":"38","author":"CM Rudin","year":"2020","journal-title":"J Clin Oncol"},{"issue":"4","key":"pone.0258605.ref013","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.jtho.2019.12.109","article-title":"Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies","volume":"15","author":"HC Chung","year":"2020","journal-title":"J Thorac Oncol"},{"key":"pone.0258605.ref014","unstructured":"US Food and Drug Administration. Pembrolizumab (KEYTRUDA) checkpoint inhibitor. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/pembrolizumab-keytruda-checkpoint-inhibitor. Published October 24, 2016.Accessed Aug 12, 2020."},{"key":"pone.0258605.ref015","unstructured":"US Food and Drug Administration. FDA grants regular approval for pembrolizumab in combination with chemotherapy for first-line treatment of metastatic nonsquamous NSCLC. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-regular-approval-pembrolizumab-combination-chemotherapy-first-line-treatment-metastatic. Published August 20, 2018. Accessed July 1, 2020."},{"key":"pone.0258605.ref016","unstructured":"US Food and Drug Administration. FDA approves pembrolizumab for metastatic small cell lung cancer. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-pembrolizumab-metastatic-small-cell-lung-cancer. Published June 18, 2019. Accessed June 11, 2020."},{"key":"pone.0258605.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lungcan.2019.01.019","article-title":"Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer","volume":"130","author":"K Zhou","year":"2019","journal-title":"Lung Cancer"},{"key":"pone.0258605.ref018","doi-asserted-by":"crossref","first-page":"602185","DOI":"10.3389\/fonc.2020.602185","article-title":"First-Line Durvalumab Plus Platinum-Etoposide Versus Platinum-Etoposide for Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis","volume":"10","author":"L Zhang","year":"2020","journal-title":"Front Oncol"},{"key":"pone.0258605.ref019","unstructured":"National Comprehensive Cancer Network. National. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer. 2020."},{"issue":"9","key":"pone.0258605.ref020","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1056\/NEJMp1405158","article-title":"Weinstein. Updating cost-effectiveness\u2014the curious resilience of the $50,000-per-QALY threshold","volume":"371","author":"PJ Neumann","year":"2014","journal-title":"N Engl J Med"},{"issue":"12","key":"pone.0258605.ref021","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1080\/13696998.2018.1521416","article-title":"Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US","volume":"21","author":"RP Insinga","year":"2018","journal-title":"Burke.J Med Econ"},{"issue":"22","key":"pone.0258605.ref022","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1056\/NEJMoa1801005","article-title":"Garassino, Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer","volume":"378","author":"L Gandhi","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0258605.ref023","unstructured":"Centers for Medicare and Medicaid Services. October 2020 ASP drug pricing files. https:\/\/www.cms.gov\/license\/ama?file=\/files\/zip\/october-2020-asp-pricing-file.zipl. Published October 3, 2020. Accessed October 20, 2020."},{"issue":"9","key":"pone.0258605.ref024","doi-asserted-by":"crossref","first-page":"e1911952","DOI":"10.1001\/jamanetworkopen.2019.11952","article-title":"Cost-effectiveness of Atezolizumab Combination Therapy for First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer in the United States","volume":"2","author":"SD Criss","year":"2019","journal-title":"JAMA Netw Open"},{"key":"pone.0258605.ref025","unstructured":"Physician Fee Schedule Search. Centers for Medicare & Medicaid Services; 2020. https:\/\/www.cms.gov\/apps\/physician-fee-schedule\/search\/search-criteria.aspx. Accessed October 2020."},{"key":"pone.0258605.ref026","unstructured":"Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. Healthcare cost and utilization project. https:\/\/hcupnet.ahrq.gov. Accessed October 12, 2020."},{"issue":"6","key":"pone.0258605.ref027","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jval.2012.04.014","article-title":"Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force\u20146","volume":"15","author":"AH Briggs","year":"2012","journal-title":"Value Health"},{"issue":"2","key":"pone.0258605.ref028","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/jamaoncol.2015.4345","article-title":"Medians and Milestones in Describing the Path to Cancer Cures: Telling \"Tails\"","volume":"2","author":"MD Hellmann","year":"2016","journal-title":"JAMA Oncol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258605","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T18:36:55Z","timestamp":1637001415000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258605"}},"subtitle":[],"editor":[{"given":"Jianxin","family":"Xue","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,11,15]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258605","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,15]]}}}