{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:55:00Z","timestamp":1770335700441,"version":"3.49.0"},"reference-count":177,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 antibodies\u2014such as nivolumab, pembrolizumab, and cemiplimab\u2014and examines pharmacokinetic\u2013pharmacodynamic (PK-PD) relationships, highlighting the impact of clearance variability on drug exposure, efficacy, and safety. Baseline clearance and its reduction during therapy, together with interindividual variability, emerge as important dynamic biomarkers with potential applicability across different cancer types for guiding individualized dosing strategies. The review also discusses established biomarkers for anti-PD-1 therapies, including tumor PD-L1 expression and immune cell signatures, and their relevance for patient stratification. The evidence supports a shift from traditional weight-based dosing toward adaptive dosing and therapeutic drug monitoring (TDM), especially in long-term responders and cost-containment contexts. Notably, the inclusion of clearance-based biomarkers\u2014such as baseline clearance and its reduction\u2014into therapeutic models represents a key step toward individualized, dynamic immunotherapy. In conclusion, optimizing anti-PD-1 therapy through PK-PD insights and biomarker integration holds promise for improving outcomes and reducing toxicity. Future research should focus on validating PK-based approaches and developing robust algorithms (machine learning models incorporating clearance, tumor burden, and other validated biomarkers) for tailored cancer treatment.<\/jats:p>","DOI":"10.3390\/cancers17193262","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:51:13Z","timestamp":1759935073000},"page":"3262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1635-8811","authenticated-orcid":false,"given":"Joaquim Faria","family":"Monteiro","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO, Unidade de Ci\u00eancias Biomoleculares Aplicadas, Laborat\u00f3rio Associado i4HB, Instituto para a Sa\u00fade e Bioeconomia, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Alexandrina","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3649-2151","authenticated-orcid":false,"given":"Diogo Gavina","family":"Tato","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Elias","family":"Moreira","sequence":"additional","affiliation":[{"name":"Servi\u00e7os Farmac\u00eauticos, Unidade Local de Sa\u00fade S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-857X","authenticated-orcid":false,"given":"Ricardo","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Clinic of Genetics and Pathology, Centro Hospitalar de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"},{"name":"Tumour and Microenvironment Interactions Group, i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-6790","authenticated-orcid":false,"given":"Henrique","family":"Reguengo","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Clinic of Genetics and Pathology, Centro Hospitalar de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-2150","authenticated-orcid":false,"given":"Jorge","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO, Unidade de Ci\u00eancias Biomoleculares Aplicadas, Laborat\u00f3rio Associado i4HB, Instituto para a Sa\u00fade e Bioeconomia, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-7798","authenticated-orcid":false,"given":"Paula","family":"Fresco","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO, Unidade de Ci\u00eancias Biomoleculares Aplicadas, Laborat\u00f3rio Associado i4HB, Instituto para a Sa\u00fade e Bioeconomia, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1146\/annurev-immunol-032414-112049","article-title":"Coinhibitory Pathways in Immunotherapy for Cancer","volume":"34","author":"Baumeister","year":"2016","journal-title":"Annu. 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