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This ancillary study used data from a systematic review conducted to identify dose\u2010finding studies for PKIs. PKIs selected for meta\u2010analyses were required to have at least five completed dose\u2010finding studies involving cancer patients, with available results, and dose escalation guided by toxicity assessment. To account for heterogeneity caused by various administration schedules, some studies were divided into study parts, considered as separate entities in the meta\u2010analyses. For each PKI, two Bayesian random\u2010effects meta\u2010analysis methods were applied to model the toxicity probability distribution of the recommended dose and to estimate the maximum tolerated dose (MTD). Meta\u2010analyses were performed for 20 PKIs including 96 studies corresponding to 115 study parts. The median posterior probability of toxicity probability was below the toxicity thresholds of 0.20 for 70% of the PKIs, even if the resulting credible intervals were very wide. All approved doses were below the MTD estimated for the minimum toxicity threshold, except for one, for which the approved dose was above the MTD estimated for the maximal threshold. The application of phase I meta\u2010analysis methods has been feasible for the majority of PKI; nevertheless, their implementation requires multiple conditions. However, meta\u2010analyses resulted in estimates with large uncertainty, probably due to limited patient numbers and\/or between\u2010study variability. This calls into question the reliability of the recommended doses.<\/jats:p>","DOI":"10.1002\/jrsm.1747","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T23:45:40Z","timestamp":1722901540000},"page":"964-977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Meta\u2010analyses of phase I dose\u2010finding studies: Application for the development of protein kinase inhibitors in oncology"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4557-3315","authenticated-orcid":false,"given":"Laura","family":"Caquelin","sequence":"first","affiliation":[{"name":"Univ Rennes, CHU Rennes, Inserm, Centre d'investigation clinique de Rennes (CIC1414), Service de Pharmacologie Clinique, Institut de Recherche en Sant\u00e9, Environnement et Travail (Irset), UMR S 1085, EHESP  Rennes 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