Cetuximab/Docetaxel Combination Shows Promise Against Advanced Non–Small-Cell Lung Cancer

November 1, 2003

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

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 trialreported at the 39th Annual Meetingof the Society of Clinical Oncology(ASCO).Edward S. Kim, MD, assistant professorof medicine in the Department of 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 22.2% when investigators talliedall 54 patients, including three whodied 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 ResultsA 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. The mediannumber of cycles was 4, with arange of 1 to 30. These data are not final: five patients are still on study.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. "We weredealing with a very sick population."He cited one man who died of anunrelated adverse event between cyclesthree and four. Although the investigatorshad recorded major shrinkageof the man's tumor, Dr. Kim saidthey could not call it a confirmedresponse.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 case of grade 4 diarrheaand two cases of grade 4 pulmonaryembolus were reported.Cetuximab did not appear to interactwith docetaxel in pharmokineticdata.