Bevacizumab/Erlotinib CombinedBoost Responses in Renal Cell Ca

NASHVILLE, Tennessee-Bevacizumab (Avastin) and erlotinib (Tarceva) in combination therapy have a high level of activity in metastatic renal cell carcinoma (RCC), according to findings from a multicenter phase II trial with the two targeted agents. David Spigel, MD, associate director of Clinical Research at the Sarah Cannon Research Institute/ Tennessee Oncology in Nashville, presented updated study results (abstract 4540). The phase II trial included 63 patients with metastatic clear cell RCC who received bevacizumab(Drug information on bevacizumab) and erlotinib daily until tumor progression. Of the 59 evaluable patients, 22% had an objective partial response using RECIST (response evaluation criteria in solid tumors) criteria and 3% had a complete response, for an overall objective response rate of 25% (Figure 1). In addition, 40% of those evaluable had stable disease and median survival time was 23 months. 'Spectacular' Responses These responses are "spectacular," noted Nicholas Vogelzang, MD, director of the Nevada Cancer Institute, Las Vegas, who discussed several presentations on targeted therapies for RCC. The 23-month median survival time was particularly impressive, he said. The drugs were well tolerated. The most common grade 3 toxicities were diarrhea, rash, nausea/vomiting, hypertension, and bleeding. Two patients discontinued treatment because of grade 3 skin toxicity, and one discontinued because of grade 4 gastrointestinal bleeding. In RCC, the von Hippel-Lindau tumor suppressor gene is inactivated, which leads to overexpression of genes that can promote tumor cell growth, including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). Bevacizumab targets VEGF and erlotinib targets the EGF receptor, while imatinib(Drug information on imatinib) (Gleevec), another targeted drug, is directed at the PDGF receptor. A three-drug combination-imatinib, bevacizumab, and erlotinib-is now being tested in a phase I/II trial led by the same group at the Sarah Cannon Research Institute (abstract 4542). So far, the findings suggest activity for the combination, though there is no indication that it will be superior to the two-drug combination. Dr. Vogelzang noted, in addition, that the toxicity of the three-drug regimen was considerably greater than that of the twodrug combination. Trials with other targeted therapies are also under way in RCC, but the drugs are at an earlier stage of development. Dr. Vogelzang pointed out that bevacizumab and erlotinib are both on the market and "presumably being used." While research will continue, he said, "certainly, standard therapy is about to change."