From Concept to Regulatory Drug Approval: Lessons for Theranostics

Radiopharmaceutical therapy is an emerging treatment modality that has demonstrated increasing importance as a significant component in the treatment of cancer. Prostate cancer (PCa) remains one of the commonest solid-organ tumors and is associated with significant societal burdens. Despite significant disease heterogeneity, PCa remains an ideal candidate for radiopharmaceutical therapy because of the prolonged disease course, metastatic disease tropism, and sensitivity to radiation therapy. To date, advanced PCa remains one of the most successful arenas for the development and approval of radiopharmaceutical agents. In this review, we aim to summarize the complex processes required to obtain regulatory approval for a novel agent and highlight the limitations and hurdles specific to the approval of radiopharmaceutical agents. In advanced PCa, we outline the importance of a framework for trial design with respect to defining dis-ease state and acceptable outcome measures-as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG). Finally, using the principles mandated by the Food and Drug Administration approval process and the framework provided by the PCWG, we out-line experience with the successful approval of the radiopharmaceuti-cal agents 223Ra and 177Lu-PSMA-617.