Early Study Shows 35% Response to SU011248 in Patients With Metastatic Renal Cell Carcinoma

January 1, 2005

This supplement to Oncology News International includes 17 reportson clinical trials of targeted therapies used alone, in combination with chemotherapy,or in combination with each other in the treatment of non–small-cell lung cancer (NSCLC),bronchoalveolar carcinoma, glioblastoma multiforme, and renal cell carcinoma.Included is a report on a novel targeted agent recently approved for treatment of NSCLC.

NEW YORK-While only about15% of patients with renal cell carcinomarespond to standard treatmentwith interferon and interleukin-2, patientsin a phase II trial of the targetedagent SU011248 showed a responserate of 35%. The trial involved patientswith metastatic renal cell cancerfor whom standard therapy had failed."This early study of SU011248 inthe treatment of renal cancer has shownmore activity as a single agent than anyother drug I've studied in the past 15years," reported Robert J. Motzer, MD,of Memorial Sloan-Kettering CancerCenter in New York (abstract 4500).SU011248 simultaneously blocksmultiple tumor growth factor receptors,including vascular endothelialgrowth factor receptor (VEGFR),platelet-derived growth factor receptor(PDGFR), KIT, and FLT3.Failed PriorCytokine TherapyDr. Motzer and colleagues testedSU011248 in 63 patients in a singlearm,multicenter trial. To be eligible,patients had to have metastatic renalcell cancer and failed one prior cytokinetherapy. Among those participating,26 patients had been treated previouslywith interferon, 19 withinterleukin-2, and 8 with interferonplus interleukin-2. Eighty-seven percentof patients had two or more sitesof metastasis, including 50% with bonemetastases and nearly 20% with livermetastases. Median age was 60 years,and the oldest patient was 87.The treatment regimen was 50 mgof daily oral SU011248 given in repeated6-week cycles of 4 weeks treatment,2 weeks rest. Treatment continueduntil disease progression ortoxicity. In 22 patients, the dose wasreduced to 37.5 to 25 mg owing tograde 3-4 toxicity, primarily includingasymptomatic amylase or lipase elevations.Limited OvertProgressionPatients' response was assessedusing RECIST (Response EvaluationCriteria in Solid Tumors) criteria. Theprimary endpoint was overall responserate.Dr. Motzer reported that 22 patients(35%) had partial responses, 22(35%) had disease stabilization lastingfor more than 3 months, and 19 (30%)had disease progression. "Very fewpatients had overt progression," hesaid."Fourteen of the partial remissionsremain durable, and patients continueon treatment (range 5.1+ to 12.0+months)," Dr. Motzer said. Mediantime to progression was 8.3 months.Probability of survival at 1 year was65%, and 43 patients are alive withmedian follow-up of 10.5 months.Toxicity included 25% grade 2 fatigueand 8% grade 3 fatigue. Fatiguewas the only adverse effect that oc-curred in more than 5% of patients."There was no hemorrhage and nohypertension," Dr. Motzer reported.Grade 3 or 4 laboratory abnormalitiesincluded 30% grade 3 lymphopeniawithout infection, 10% grade 3neutropenia, and 2% grade 4 neutropenia,21% elevated lipase, 8% elevatedamylase without clinical signs ofpancreatitis, and 8% fatigue/asthenia.Two patients were taken off the studybecause of decreases in left ventricularejection fraction of > 20% withoutclinical symptoms.Prolonged Timeto ProgressionTime to progression was 8.3months with SU011248 vs 4.8 monthsin historical data with bevacizumaband 2.5 months with placebo."SU011248 was well tolerated whengiven once daily by oral administrationon a 4-weeks-on/2-weeks-offschedule. A high level of antitumoractivity was demonstrated by a 35%partial response rate. Also, antitumoractivity was suggested by a prolongedmedian time to progression of8.3 months compared to historicalcontrols," Dr. Motzer said. "The antitumoreffect was demonstrated as asecond-line therapy following cytokinefailure, a setting where no effectivesystemic therapy exists."SU011248 is now in phase III trialsvs interferon for first-line treatmentof advanced kidney cancer and isalso being investigated in a confirmatorysingle-arm phase III trial assecond-line therapy, Dr. Motzer toldOncology News International.