{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:12:58Z","timestamp":1775610778478,"version":"3.50.1"},"reference-count":14,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Programmed death or ligand\u20101 (PD\u2010(L)1) pathway inhibitors confer improved survival as the first\u2010line treatment for advanced non\u2010small cell lung cancer (aNSCLC) in patients with PD\u2010L1 expression (PD\u2010L1\u2009+\u2009e\u2009\u2265\u200950%) compared to platinum\u2010doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients with PD\u2010L1\u2009+\u2009e of \u226550% receiving pembrolizumab monotherapy, very high levels of PD\u2010L1\u2009+\u2009e (\u226590%) may be associated with better outcomes. We sought to assess whether very high PD\u2010L1\u2009+\u2009e (\u226590%) compared to high PD\u2010L1\u2009+\u2009e (50%\u201389%) is associated with an overall survival benefit in aNSCLC patients receiving anti\u2010PD\u2010(L)1 monotherapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a single\u2010site retrospective cohort study of aNSCLC patients who initiated PD\u2010(L)1 inhibitor monotherapy as the first\u2010line treatment from October 24, 2016, to August 25, 2021, and had a PD\u2010L1\u2009+\u2009e\u2009\u2265\u200950%. The primary outcome was overall survival, measured from the start of the first\u2010line PD\u2010(L)1 inhibitor monotherapy (index date) to date of death or last confirmed activity prior to the cohort exit date. Propensity score\u2010based inverse probability weighting (IPW) was used to control for confounding in Kaplan\u2013Meier curves and Cox proportional hazard regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred sixty\u2010six patients with aNSCLC receiving PD\u2010(L)1 inhibitor monotherapy met inclusion criteria. 54% were female, 90% received pembrolizumab, median age was 68\u2009years, 70% had non\u2010squamous cell carcinoma, 94% had a history of smoking, 29% had a KRAS mutation, and 37% had very high PD\u2010L1\u2009+\u2009e. Unweighted covariates at cohort entry were similar between groups (absolute standardized mean differences [SMDs] &lt;0.1) except for race (SMD\u00a0=\u00a00.2); age at therapy initiation (SMD\u00a0=\u00a00.13); smoking status (SMD\u00a0=\u00a00.13), and BRAF mutation status (SMD\u00a0=\u00a00.11). After weighting, baseline covariates were well balanced (all absolute SMDs &lt;0.1). In the weighted analysis, having a very high PD\u2010L1\u2009+\u2009e was associated with lower mortality (weighted hazard ratio 0.57, 95% CI 0.36\u20130.90) and longer median survival: 3.85 versus 1.49\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Very high PD\u2010L1\u2009+\u2009e (\u226590%) was associated with an overall survival benefit over high PD\u2010L1\u2009+\u2009e (50%\u201389%) in patients receiving the first\u2010line PD\u2010(L)1 inhibitor monotherapy in a model controlling for potential confounders. These findings should be confirmed in a larger real\u2010world data set.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5487","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T07:55:18Z","timestamp":1654588518000},"page":"1121-1126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Very high <scp>PD\u2010L1<\/scp> expression as a prognostic indicator of overall survival among patients with advanced <scp>non\u2010small<\/scp> cell lung cancer receiving anti\u2010<scp>PD<\/scp>\u2010(L)1 monotherapies in routine practice"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3450-4843","authenticated-orcid":false,"given":"Mohsin","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca A.","family":"Hubbard","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronac","family":"Mamtani","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melina E.","family":"Marmarelis","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Hennessy","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2020-206709"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","unstructured":"ReckM Rodriguez\u2010AbreuD RobinsonA et al.Updated analysis of KEYNOTE\u2010024: pembrolizumab versus platinum\u2010based chemotherapy for advanced non\u2010small\u2010cell lung cancer with PD\u2010L1 tumor proportion score of 50% or 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