Bevacizumab/Erlotinib CombinedBoost Responses in Renal Cell Ca

NASHVILLE, Tennessee-Bevacizumab(Avastin) and erlotinib(Tarceva) in combination therapyhave a high level of activity in metastaticrenal cell carcinoma (RCC),according to findings from a multicenterphase II trial with the two targetedagents. David Spigel, MD, associatedirector of Clinical Research atthe Sarah Cannon Research Institute/Tennessee Oncology in Nashville, presentedupdated study results (abstract4540).The phase II trial included 63 patientswith metastatic clear cell RCCwho received bevacizumab and erlotinibdaily until tumor progression. Ofthe 59 evaluable patients, 22% had anobjective partial response using RECIST(response evaluation criteria insolid tumors) criteria and 3% had acomplete response, for an overall objectiveresponse rate of 25% (Figure1). In addition, 40% of those evaluablehad stable disease and median survivaltime was 23 months.'Spectacular' ResponsesThese responses are "spectacular,"noted Nicholas Vogelzang, MD, directorof the Nevada Cancer Institute,Las Vegas, who discussed several presentationson targeted therapies forRCC. The 23-month median survivaltime was particularly impressive, hesaid.The drugs were well tolerated. Themost common grade 3 toxicities werediarrhea, rash, nausea/vomiting, hypertension,and bleeding. Two patientsdiscontinued treatment because ofgrade 3 skin toxicity, and one discontinuedbecause of grade 4 gastrointestinalbleeding.In RCC, the von Hippel-Lindau tumorsuppressor gene is inactivated,which leads to overexpression of genesthat can promote tumor cell growth,including vascular endothelial growthfactor (VEGF), epidermal growth factor(EGF), and platelet-derived growthfactor (PDGF).Bevacizumab targets VEGF and erlotinibtargets the EGF receptor, whileimatinib (Gleevec), another targeteddrug, is directed at the PDGF receptor.A three-drug combination-imatinib,bevacizumab, and erlotinib-is nowbeing tested in a phase I/II trial led bythe same group at the Sarah CannonResearch Institute (abstract 4542). Sofar, the findings suggest activity for thecombination, though there is no indicationthat it will be superior to thetwo-drug combination. Dr. Vogelzangnoted, in addition, that the toxicityof the three-drug regimen was considerablygreater than that of the twodrugcombination.Trials with other targeted therapiesare also under way in RCC, but thedrugs are at an earlier stage of development.Dr. Vogelzang pointed out thatbevacizumab and erlotinib are bothon the market and "presumably beingused." While research will continue,he said, "certainly, standard therapy isabout to change."