Oncology Drug Approvals: Evaluating Endpoints and Evidence in an Era of Breakthrough Therapies

In the past few decades, with improved understanding of the genomic and immunologic underpinnings of cancer, better molecular characterization of tumors, and more precisely targeted agents, new and innovative therapeutics have altered the natural histories of certain cancer types such as chronic myeloid leukemia (CML), multiple myeloma, and melanoma. Recognizing a need to further expedite development of drugs that show promising early clinical evidence of benefit over available therapy, the U.S. Congress, in 2012, established the Breakthrough Therapy Designation program [1]. The U.S. Food and Drug Administration (FDA) uses this program frequently for transformative therapies that show great promise in early clinical trials [2]. Table 1 provides examples of new FDA-approved therapies that were developed based on the improved understanding of tumor biology and that markedly changed the therapeutic landscape of certain cancer types. Figure 1 highlights certain cancer types where 5-year survival has improved in recent decades, which is at least partially attributed to better therapeutic options. With the Breakthrough Therapy Designation program adding to the tools that the FDA has for expediting drug development, the FDA reassessed the endpoints needed for approval of transformative therapies. Although the demonstration of an improvement in overall survival remains the gold standard for drug approval, innovation in cancer research has led to use of other endpoints in regulatory decision-making. These endpoints include substantially delaying tumor progression or extending progression-free survival, substantially reducing tumor size for a prolonged time, improving objective response rate and duration of response, or improving cancer-related symptoms and patient function. © AlphaMed Press.