{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:20:07Z","timestamp":1783948807017,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Programmed cell death (PD) protein (ligand [L])\u20101 inhibitors are established treatments for metastatic non\u2010small cell lung cancer (mNSCLC). In oncology, progression\u2010free survival (PFS) and objective response rate (ORR) are often used as surrogates for overall survival (OS) to inform clinical development; however, there remains uncertainty in the concordance between these endpoints. This study evaluated the impact of a broad set of PD\u2010(L)1 inhibitors on efficacy, explored the relationship between ORR and survival endpoints, and compared PD\u20101 and PD\u2010L1 treatments for mNSCLC. A dataset of 114 studies was used to conduct a sequential two\u2010stage model\u2010based meta\u2010analysis (MBMA). Firstly, an MBMA with mixed\u2010effects logistic regression was applied to evaluate treatment\u2010specific and clinical covariate effects on ORR. Secondly, MBMAs for OS and PFS were conducted with a mixed\u2010effects semi\u2010parametric proportional hazard approach using digitized Kaplan\u2013Meier curves, with the treatment type, covariates, and ORR as inputs. ORR was demonstrated to be a significant predictor of OS and PFS. Simulations of head\u2010to\u2010head comparisons of treatment types were conducted using these models. Trends in predicted outcomes numerically favored PD\u20101 over PD\u2010L1 treatments, but differences were not statistically significant. These findings support evidence\u2010based decision\u2010making for late\u2010stage trial designs using ORR data from earlier phase trials, enabling benchmarking of emerging data by adjusting for explained and unexplained sources of variability in existing and emerging data.<\/jats:p>","DOI":"10.1002\/psp4.70196","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:59:57Z","timestamp":1771487997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Model\u2010Based Meta\u2010Analysis of Objective Response Rate and Survival Endpoints to Compare\n                    <scp>PD<\/scp>\n                    \u20101 and\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Treatment Outcomes in Non\u2010Small Cell Lung Cancer"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-3730","authenticated-orcid":false,"given":"Richard C.","family":"Franzese","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GSK  Upper Providence Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5002-3372","authenticated-orcid":false,"given":"Li","family":"Qin","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-3030","authenticated-orcid":false,"given":"Shuai","family":"Fu","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rich","sequence":"additional","affiliation":[{"name":"InnoMx  Outremont Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3389-7175","authenticated-orcid":false,"given":"Eleftherios","family":"Zografos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GSK  Upper Providence Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-9157","authenticated-orcid":false,"given":"Matthew L.","family":"Zierhut","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2186-7195","authenticated-orcid":false,"given":"Sandra A. G.","family":"Visser","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GSK  Upper Providence Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"D.Planchard S.Popat K.Kerr et\u00a0al. \u201cMetastatic Non\u2010Small Cell Lung Cancer: ESMO Clinical Practice Guidelines for Diagnosis Treatment and Follow\u2010Up \u201dAnnals of Oncology29 (2018): iv192\u2013iv237.","DOI":"10.1093\/annonc\/mdy275"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/OP.24.00177"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00225"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00040-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.10.011"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-018-2738-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12917"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2022.06.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1902"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S242097"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03201-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2019.1674452"},{"key":"e_1_2_9_14_1","unstructured":"Certara \u201cCODEx PD\u20101 Solid Tumors (PD1ST) Clinical Outcomes Database \u201daccessed December 24 2022 https:\/\/codex.certara.com\/codex\/pd\u20101\u2010solid\u2010tumors\/."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-12-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1956"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.5367"},{"key":"e_1_2_9_19_1","first-page":"1546","article-title":"How to Differentiate Pseudoprogression From True Progression in Cancer Patients Treated With Immunotherapy","volume":"9","author":"Ma Y.","year":"2019","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2019.0144"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2020200443"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70196","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70196","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70196","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:22:11Z","timestamp":1773807731000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/psp4.70196"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70196","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"2025-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70196"}}