Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials Journal Article
| Authors: | Yokota, T.; Bendell, J.; Lorusso, P.; Tsushima, T.; Desai, V.; Kenmotsu, H.; Watanabe, J.; Ono, A.; Murugesan, B.; Silva, J.; Naito, T.; Greenberg, J.; Kumar, P.; Wang, Y.; Jikoh, T.; Shiga, R.; Hyman, D. M.; Ho, A. L.; Spriggs, D. R.; Schwartz, G. K.; Gounder, M. M. |
| Article Title: | Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials |
| 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. © 2018 The Author(s). |
| Journal Title: | British Journal of Cancer |
| Volume: | 118 |
| Issue: | 12 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-06-01 |
| Start Page: | 1571 |
| End Page: | 1579 |
| Language: | English |
| DOI: | 10.1038/s41416-018-0102-1 |
| PROVIDER: | scopus |
| PUBMED: | 29795308 |
| PMCID: | PMC6008299 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 July 2018 -- Source: Scopus |
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