Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials
Year: 2018
Type: article
Abstract: BACKGROUND: We examined the impact of race on the maximum tolerated doses (MTD) and final approved doses (FAD) of single-agent molecular-targeted agents (MTA) in North America/Europe (NA/EU) and Asia. METHODS: We searched PubMed and regulatory databases to identify targeted drugs approved globally and compared their FAD and MTD in corresponding phase I/II studies conducted separately in NA/EU and Asia. To evaluate this further, we conducted parallel, prospective, first-in-human studies of DS-7423, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumours in the US and Japan. We pooled and compared the pharmacokinetics (PK), pharmacodynamics (PD), toxicity, and efficacy between these populations. RESULTS: 17 MTA were approved in NA/EU and Asia from 2001 to 2015. Recommended phase 2 doses (RP2D) were identical across races in 14 of 17 (80%) studies and differences were not clinically meaningful. FAD were identical across all regions. 42 and 27 patients from US and Japan, respectively, were enrolled in the phase I studies of DS-7423. Despite differences in race, body weight, and body mass index, the RP2D were 240 mg/day with no differences in toxicities, PK, PD, or efficacy. CONCLUSIONS: Conducting separate clinical trials of single-agent MTA in Caucasian and Asian populations may be redundant.
Source: British Journal of Cancer
Authors: Tomoya Yokota, Johanna Bendell, Patricia LoRusso, Takahiro Tsushima, Ved Desai, Hirotsugu Kenmotsu, Junichiro Watanabe, Akira Ono, Bhavani Murugesan, Joseph Silva, Tateaki Naito, Jonathan Greenberg, Prasanna Kumar, Yibin Wang, Takahiro Jikoh, Ryota Shiga, David M. Hyman, Alan Loh Ho, David R. Spriggs, Gary K. Schwartz, Mrinal M. Gounder
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
Funder: National Cancer Institute
Award: Cancer Center Support Grant
OpenAlex ID: W2804740856