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Br J Cancer. 2018 Jun;118(12):1571-1579. doi: 10.1038/s41416-018-0102-1. Epub 2018 May 24.

Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials.

Author information

1
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
2
Sarah Cannon Research Institute/Tennessee Oncology, 250 25th Ave N Suite 200, Nashville, TN, 37203, USA.
3
Yale University, 55 Park Street, Ste First Floor, New Haven, CT, 06519, USA.
4
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, 10065, USA.
5
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
6
Division of Breast Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
7
Daiichi Sankyo, Inc., 399 Thornall Street, Edison, NJ, 08837, USA.
8
Daiichi Sankyo, Inc., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
9
Division of Hematology/Oncology, Columbia University, 161 Fort Washington Avenue (Floor 9), New York, NY, 10032, USA.
10
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, 10065, USA. gounderm@mskcc.org.

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.

PMID:
29795308
PMCID:
PMC6008299
DOI:
10.1038/s41416-018-0102-1
[Indexed for MEDLINE]
Free PMC Article

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