Oncology Drug Development and Approval of Systemic Anticancer Therapy by the U.S. Food and Drug Administration

Background. Regulatory approval of oncology drugs is the cornerstone of the development process and approval characteristics shape eventual utilization. Approval trends and characteristics provide valuable information for drug developers and regulators and ultimately affect clinicians and patients. Methods. Indication characteristics were tabulated for drugs approved by the U.S. Food and Drug Administration (FDA) for systemic therapy of malignancies from 1949 through October 2011. Variables included time to approval, initial/supplemental indication, tumor type, stage of disease, specification of protein expression or genetic information, drug class, trial design, concomitant agent, trial size, and endpoint. Results. A total of 121 unique anticancer agents, including 242 unique indications, were approved. The number of trials for each indication has decreased; however, trial size has increased and more randomized controlled trials have been performed. Trial designs have increasingly used time‐to‐event endpoints and rarely have used symptom‐based primary endpoints. Approvals have been primarily single agent, with less emphasis on palliative treatments and increasing emphasis on advanced disease stages and requirements for prior therapy. Molecular specifications in labels have increased, but they are present in less than 30% of recent indications and are not associated with shorter approval times. Conclusion. Approval of oncology agents is occurring in increasingly more challenging settings, suggesting gaps between eventual practice and development in potentially suboptimal indications. Molecular specifications promise to enhance development, yet widespread use in label indications has not yet been achieved.