Emerging oncology drug targets in the 21st century: An FDA analysis.

Abstract

e14067 Background: Traditional chemotherapy agents are cytotoxic and typically act on all rapidly dividing cells. In contrast, targeted cancer therapies take advantage of unique genetic or proteomic susceptibility in cancer cells, their microenvironment, or the immune system to selectively target tumor tissue or stimulate immune activity. We catalogued oncology drug approvals in the U.S. in the 21st century to study the evolution of molecular targets over the last twenty years. Methods: We used internal FDA databases and data repositories to generate a dataset of all oncology approvals granted 1/1/2000-12/31/2019. This dataset was curated through a comprehensive survey of drug labels, drug reviews, and published literature to include target gene(s), mechanism of action, drug class, and approved indications for each drug. Approvals were grouped into five-year periods for trend analyses. Results: There has been an increase in the number of oncology approvals over the last twenty years, the vast majority of which are targeted therapies. There have been considerable recent advances in some disease sites. Three disease sites (ovary, bladder, and liver) had many approvals in the last five years after few to none 2000-2014; lung cancer and melanoma have seen substantial advances in the last ten years. Additionally, the first site-agnostic approvals occurred in the last five years. Kinase inhibitors are the most common drug class by both number of drugs and indications. Immune checkpoint inhibitors (ICI) are the second most common class by number of indications, despite having only entered the market in 2011 and being the sixth most common class by number of drugs. The target gene PD-1 has the highest number of approved indications, followed by EGFR and the BCR-ABL fusion gene. The number of novel genes targeted by drugs approved in 2010-2019 is nearly double that of 2000-2009, with the most novel gene targets in 2019 (n = 7). Conclusions: This analysis captures the landscape of targeted drug approvals in the 21st century, including the continued dominance of kinase inhibitors despite the dramatic impact of ICIs on cancer care since their introduction in 2011. The promise of targeted therapy in oncology is especially evident from the introduction of site-agnostic indications, new approvals in cancer types with limited therapy options, and ICIs with many indications due to targeting tumors indirectly via the immune system. The continual introduction of novel gene targets provides a snapshot of ongoing novel drug development, and it will be interesting to see whether this trend continues over the next twenty years.