FDA Guidance on the Use of Pathologic Complete Response in Development of New Treatments for High-Risk Early Breast Cancer Includes ASCO Suggestions

The U.S. Food and Drug Administration’s (FDA) final Guidance for Industry on Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer incorporates two changes that ASCO had proposed in comments submitted to the agency on a draft guidance issued in 2012.

The guidance is intended to assist sponsors in designing trials to support marketing approval of drugs and biological products for treating breast cancer in the neoadjuvant setting. The document addresses the use of pathologic complete response in breast cancer as a potential endpoint to support provisional approval under the accelerated approval regulations.

Two areas where FDA made changes consistent with ASCO’s suggestions included:

• Definition of Pathologic Complete Response: FDA removed ductal carcinoma in situ as a consideration for the definition of pathologic complete response.
• Feasibility of Expected pCR Rates: FDA modified the section to focus on comparing pathologic complete response of standard therapy with the investigational agent, saying that a large difference is a reasonable proxy for improvements in overall survival.

ASCO cosponsored a workshop with FDA in 2013 on pathologic complete response in high-risk early-stage breast cancer. The guidance includes a statement about implementation that discusses the workshop’s conclusion that the benefits of using pathologic complete response as a measure for accelerated approvals outweigh the risks.

Read the guidance at: www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm305501.pdf ■