Invited Commentary: Response Rate as an Approval End Point in Oncology: Back to the Future

JAMA (part comments plus page 1 - full access requires $$)

Overall response rate (ORR) as a surrogate end point in oncology drug approval has a long history. In the 1970s, the US Food and Drug Administration (FDA) usually approved drugs on the basis of ORR. In the 1980s, after discussions with the Oncologic Drug Advisory Committee, the FDA determined that cancer drug approval should be based on more direct evidence of clinical benefit, such as improvements in overall survival (OS), tumor-related symptoms, or physical function.1 In the past decade, due to an improved understanding of the genomic underpinnings of cancer, better molecular characterization of tumors, and more precisely targeted agents, unprecedented rates of response have radically altered the therapeutic landscape in a number of malignant neoplasms. Therefore, ORR and duration of response as assessed in single-arm trials has served as the basis of accelerated approval and at times regular approval in a number of refractory malignant neoplasms, including non–small-cell lung cancer (NSCLC), lymphoma, melanoma, and myeloma.