Cetuximab/Docetaxel Combination Shows Promise Against Advanced NSCLC

HOUSTON-More than20% of patients resistant to secondlinechemotherapy for advanced non-small-cell lung cancer (NSCLC) respondedto a combination ofcetuximab (Erbitux) and docetaxel(Taxotere) in a phase II clinical trial.Edward S. Kim, MD, assistant professorof medicine of the Departmentof Thoracic Oncology, Head and NeckMedical Oncology, at the Universityof Texas M. D. Anderson Cancer Center,Houston, reported a 28% responserate in 47 evaluable patients. The ratewas to 22.2% when investigators talliedall 54 patients, including threewho died of unrelated adverse events(ASCO abstract 2581).The only approved chemotherapyfor second-line NSCLC is docetaxel,Dr. Kim noted. Although docetaxelhas been shown to produce a responserate as high as 21%, he told ONI that15% or less is more typical for platinum-refractory NSCLC patients.Concerning the cetuximab plusdocetaxel combination, Dr. Kim said,"In a limited study, there is encouragingactivity, and it warrants furtherinvestigation in a randomized setting.Is this going to cure cancer? Probablynot. Could it help people live longer?Very possibly."Continued support of the investigationis uncertain, Dr. Kim noted.The issue is not scientific merit, butallocating limited resources, he said,expressing hope that funds could befound for a second randomized phaseII study if a full phase III trial were notpossible at this time.Phase II Results
A monoclonal antibody, cetuximabtargets the HER1/epidermal growthfactor receptor (HER1/EGFR), whichis expressed in lung cancer and manyother solid tumors. Patients in thephase II trial received 400 mg/m² ofcetuximab intravenously the first weekand 250 mg/m² every week thereafter.They were given 75 mg/m² of docetaxelintravenously every 3 weeks.One patient had a complete response,and 11 had partial responses.Another 18 had progressive disease,and 7 were not evaluable.Median progression-free survivalwas reported at 2.6 months for the fullcohort; median overall survival was7.5 months. The median time to diseaseprogression was 89 days. Themedian number of cycles was 4 with arange of 1 to 30 with several patientsstill on study. These data are not final,however, as five patients are still onstudy.Dr. Kim added that the results areparticularly encouraging in light ofthe poor condition of the study population.The trial not only restrictedenrollment to EGFR-positive patientswho were actively failing chemotherapy,but it also insisted that patientshave had disease recurrence within 3months of their last chemotherapy."We wanted to focus on those patientswho were actively progressing on chemotherapy,"Dr. Kim said, adding,"We were dealing with a very sick population."He cited one man who died of anunrelated adverse event between cyclesthree and four. Although the in-vestigators had recorded major shrinkageof the man's tumor, Dr. Kim saidthey could not call it a confirmed response.Four patients discontinued becauseof allergic reactions but the regimenwas reported to be well tolerated withminimal toxicity. Infection in 21% ofpatients, fatigue in 21%, and rash in19% were the most common grade 3toxicities. One grade 4 diarrhea andtwo cases of grade 4 pulmonary emboluswere reported.Cetuximab did not appear to interactwith docetaxel in pharmokineticdata.