Dr. Burris Discusses Pathological CR as an Endpoint

Howard A. "Skip" Burris, III, MD, chief medical officer and executive director, Drug Development Program, Sarah Cannon Research Institute in Nashville, Tennessee, discusses the use of pathological complete response (pCR) as an endpoint for clinical trials. Burris explains that pCR is controversial as an endpoint for neoadjuvant studies. In trials examining traditional chemotherapy, a treatment that rapidly kills malignant cells, it has demonstrated some efficacy as an endpoint. In trials investigating biologics it becomes a mixed story, especially when the biologics are combined with hormonal therapies. The phase II, neoadjuvant study of letrozole plus everolimus in estrogen receptor-positive breast cancer showed a decrease in the proliferation marker Ki-67 but the pCR was only 1%. The pCR was very low but was consistent with other trials investigating neoadjuvant endocrine therapy. The results from this trial were used as the foundation for the phase III BOLERO-2 study that showed a significant improvement in metastatic breast cancer with the addition of everolimus to aromatase inhibitors. If pCR were used as an endpoint in the letrozole and everolimus trial the results of BOLERO-2 would never have been realized. Although pCR can provide some useful information, it can be misleading as an endpoint.