In Response: The letter to the Editor from Dr. Jubb has raised an important question as to whether the objective response rate is a useful indicator of treatment benefit from bevacizumab (BV) in combination with chemotherapy. Whether the response rate and progression-free survival are surrogates for overall survival (clinical benefit) have stimulated much discussion in clinical oncology research. The objective response in solid tumors is evaluated by measuring the reduction of existing tumors and, in some cases, is associated with an improvement in overall survival (1). In one phase III trial of BV plus chemotherapy as first-line treatment in metastatic colorectal cancer, the addition of BV significantly increased the objective response and improved overall survival (2). In a second first-line trial in metastatic colorectal cancer, the addition of BV significantly improved progression-free survival but not response rate and survival (3). An increase in both objective response rate and survival were observed in patients with non–small cell lung cancer treated with BV plus chemotherapy versus chemotherapy alone as first-line treatment (4). Recently, in a phase III trial of paclitaxel versus paclitaxel plus BV as first-line therapy in metastatic breast cancer, the addition of BV significantly improved progression-free survival and response rate but not overall survival (5). The latter could have been confounded by the administration of multiple effective therapies after first-line treatment, making it difficult to determine the effect on survival of the initial regimen. Because our study was a very small pilot study, survival was not an end point. However, Dr. Jubb's point is well-taken. The angiogenic biomarkers vascular endothelial growth factor A, CD31, platelet-derived growth factor receptor β, and others need to be studied in large prospective trials to determine the utility of these markers to predict outcome as we mentioned in the discussion. It is anticipated that validated biomarkers will guide the selection of patients who will benefit from antiangiogenic agents in combination with chemotherapy such as vascular endothelial growth factor genotype (6). This is clearly one of the most needed areas of research in cancer treatment today in the era of targeted therapy and, hence, personalized medicine.
Disclosure of Potential Conflicts of Interest
S.M. Swain's institution has received research grants from Genentech and she has been compensated for travel to the investigator meetings by Genentech.