Improved understanding of the molecular basis of cancer has led to the discovery of several new therapies, which, in some cases, have demonstrated substantial anti-tumor activity in early phase trials and subsequently improved overall survival (OS). In 2012, the breakthrough therapy designation was established to expedite the development of US Food and Drug Administration (FDA) approval of such therapies as well as promising new medications intended to treat other serious or life-threatening conditions. A drug may receive this designation if preliminary clinical evidence suggests a substantial improvement in a clinically significant endpoint over available treatments; a clinically significant endpoint may include not only survival but also surrogate endpoints or biomarkers likely to predict a clinical benefit. This designation provides many benefits to sponsors, such as intensive guidance from the FDA throughout the drug development process, which results in significantly faster development and regulatory review times. Since its creation in 2012, the breakthrough therapy designation program has grown rapidly, with more than 30 cancer drug approvals receiving designations to date. However, the clinical benefit and cost of breakthrough-designated cancer drugs are uncertain.

The prices of cancer drugs at market entry have grown substantially over the years. At the same time, regulatory approval of cancer drugs has relied increasingly on surrogate endpoints. A prior study, which focused on new drug approvals, found no statistically significant advantage in efficacy or safety for breakthrough-designated cancer therapies versus non–breakthrough-designated cancer therapies.