Tohoku J. Exp. Med., 2013 May, 230(1)

Perspective

Clinical Classification of Targeted Agents Used for Anticancer Treatment

IKUO SEKINE¹ and YUICHI TAKIGUCHI¹

¹Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan

The introduction of targeted agents has resulted in a breakthrough in advanced cancer treatment. We propose a new classification for these agents to evaluate them in appropriate clinical trials according to agent class. Class I agents that inhibit driver oncogene activities result in massive and rapid tumor shrinkage, with response rates as high as 70% when administered to patients with appropriate targets. These agents can be evaluated in single-arm phase II trials with response rate as the primary endpoint. Class II agents inhibit one oncogene that is partially responsible for accelerating tumor cell proliferation. Their clinical features include synergism with cytotoxic agents and moderate single-agent activity, as shown by response rates of between 10% and 30%. Randomized phase II trials in patients with over-expressed targets are appropriate for the evaluation of these agents. Class III agents inhibit proliferation regulators that are not always oncogenic. Their clinical activity is unique, as they confer a survival benefit on patients with a minimum tumor shrinkage effect. Class IV agents target environmental molecules that act on normal cells surrounding tumor cells, such as the endothelial cells that form vessels. Placebo-controlled randomized phase II trials are required to identify the clinical activities of both class III and IV agents. Class V agents act by enhancing anti-tumor immunity. Immune-related response criteria should aid the evaluation of these agents. We believe that this classification for targeted agents should facilitate their further clinical development.

keywords —— clinical trial design; driver mutations; targeted agents; oncogene addiction; targeted cancer therapy

© 2013 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2013, 230, 1-5

Correspondence: Ikuo Sekine, Department of Medical Oncology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan.

e-mail: isekine@chiba-u.jp