Scientific Publications by FDA Staff

Clin Cancer Res 2020 Jul 30 [Epub ahead of print]

Regulatory considerations for contribution of effect of drugs used in combination regimens: renal cell cancer case studies.

Brewer JR, Chang E, Agrawal S, Singh H, Suzman DL, Xu J, Weinstock C, Fernandes LL, Cheng J, Zhang L, Xie D, Goldberg KB, Bloomquist EW, Tang S, Sridhara R, Theoret MR, Pazdur R, Ibrahim A, Beaver JA

The development and review of combination drug regimens in oncology may present unique challenges to investigators and regulators. For regulatory approval of combination regimens, it is necessary to demonstrate the contribution of effect of each monotherapy to the overall combination. Alternative approaches to traditional designs may be needed to accelerate oncology drug development, for example when combinations are substantially superior to available therapy, to reduce exposure to less effective therapies, and for drugs that are inactive as single agents and that in combination potentiate activity of another drug. These approaches include demonstration of activity in smaller randomized trials and/or monotherapy trials conducted in a similar disease setting. This article will discuss alternative approaches used in development of approved drugs in combination, based on examples of recent approvals of combination regimens in renal cell carcinoma.