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Yet, their role in guiding recommended phase II dose (RP2D) decisions remains unclear. Therefore, this review evaluates how pharmacodynamic analyses assisted the determination of the recommended phase II dose (RP2D) in first-in-human cancer trials of small-molecule agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>First-in-human dose finding clinical trials of single-agent small-molecule anticancer therapies published between 2022 and 2025 that included pharmacodynamic assessments, were investigated. Clinical trials were evaluated for correlation of pharmacodynamic results at the analyzed doses and their influence in the RP2D decision-making process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 535 records were identified and 34 articles, reporting on 34 separate trials, were included. A correlation was found between the pharmacodynamic results and the analyzed dose levels in 92% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931\/34). However, only half of the clinical trials (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917\/34) reported their pharmacodynamic results in the RP2D decision-making process, while 41% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914\/34) did not. In most of the clinical trials that did not use their pharmacodynamic results in the RP2D decision-making process, only one pharmacodynamic analysis was performed (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099\/14, 64%) and they often determined their RP2D solely based on safety and\/or tolerability (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097\/14, 50%). Invasive procedures were often performed without clear utilization of pharmacodynamic data, raising ethical considerations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings underscore the need for appropriate sample sizes planning and validated, fit-for-purpose pharmacodynamic assays to ensure meaningful use in dose selection, optimizing patient benefit and trial design.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00280-026-04924-7","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:34:30Z","timestamp":1783316070000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The use of pharmacodynamic results for recommended phase II decision making in oncology clinical trials"],"prefix":"10.1007","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7498-7912","authenticated-orcid":false,"given":"A. 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TS provided speaker, consultation or attended advisory boards for MedHealth Communications B.V., GENASE therapeutics, Ellipses pharma; Revealis Biotherapeutics; Support for attending investigator meetings: GCP-Service International Ltd. & Co. KG on behalf of EPICS therapeutics, MSD. All outside the submitted work, all payment to the Netherlands Cancer Institute. NS provided consultation or attended advisory boards for Boehringer Ingelheim, Bristol-Myers Squibb, Ellipses Pharma, GlaxoSmithKline, Incyte; received research grants from Abbvie, Actuate Therapeutics, Amgen, Anaveon, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, CellCentric, Cogent Biosciences, Cresecendo Biologics, Deciphera, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, Janssen, Kling Biotherapeutics, Lixte, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Novartis, Pfizer, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho, Zentalis. 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