The Evolution of Clinical Trials in Metastatic Breast Cancer: Design Features and Endpoints That Matter.

ABSTRACT

The evolution of thought in assessing benefit in clinical trials of systemic therapy for metastatic breast cancer (MBC) is well documented, with most agents garnering regulatory approval based either on an advantage in overall survival (OS), time to progression (TTP), or progression-free survival (PFS) over an existing standard of care or objective response rate (ORR). Previous guidance for industry on clinical trial endpoints for the approval of cancer drugs and biologics was provided by the U.S. Food and Drug Administration (FDA) in 2007 and recently updated in 2018. The more recent FDA guidance recognizes that advances in science are facilitating the development of oncology products, which "may also result in the identification of additional endpoints that may be used to support approval of oncology products." This article critically addressed the evolution of thought on the advancement of clinical trials in MBC, from various stakeholder perspectives. Despite the term "stakeholder," the objective of all co-authors and parties concerned is to promote and inform the optimal design, conduct, and reporting of clinical trials for women with advanced breast cancer toward improving and extending lives. This article provides an overview of the evolving perspectives on this issue from the physician, regulatory agency, and patient and/or advocate points of view.