Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2025

Autores

Joaquim Monteiro (Autor) FFUP; Fernandes, A (Autor) Outra; Tato, DG (Autor) Outra; Moreira, E (Autor) Outra; Ribeiro, R (Autor) Outra; Reguengo, H (Autor) Outra; Goncalves, J (Autor) FFUP; Fresco, P (Autor) FFUP

Revista

Título: Cancers

Vol. 17

Página Final: 3262

ISSN: 2072-6694

Editora: MDPI

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-01A-7DG

DOI: 10.3390/cancers17193262

Abstract (EN): Simple Summary The purpose of this review is to explore the therapeutic optimization of anti-PD-1 drugs by focusing on pharmacokinetic (PK) principles. The article discusses how interpatient variability and tumor burden affect drug exposure and highlights the PK-pharmacodynamic relationship in terms of exposure-efficacy and exposure-safety. It emphasizes the role of clearance variability, particularly baseline clearance and its dynamic reduction during treatment, as relevant biomarkers for stratifying patients and guiding individualized dosing strategies. The review also examines current dosing approaches, including fixed versus weight-based regimens, and emerging strategies such as therapeutic drug monitoring and PK-guided personalization. By integrating PK data, clearance biomarkers, and clinical outcomes, the review supports a shift toward more adaptive and personalized use of anti-PD1 therapies aimed at maximizing therapeutic benefit while minimizing adverse effects.Abstract 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-such as nivolumab, pembrolizumab, and cemiplimab-and examines pharmacokinetic-pharmacodynamic (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-such as baseline clearance and its reduction-into 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 26