Radiation Therapy Oncology Group (RTOG) investigators and ImClone Systems have added the biologic agent cetuximab (Erbitux) to chemotherapy and radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC), resulting in higher survival rates, according to results presented at the 2008 American Society of Clinical Oncology (ASCO) meeting in Chicago this week.
Cetuximab is an IgG1 monoclonal antibody that targets the epidermal growth factor receptor (EGFR), thereby inhibiting cancer cell growth and proliferation, according to the researchers. They said that cetuximab has been shown to enhance the activity of radiation therapy.
The phase II study of 87 evaluable patients with Stage IIIA/B inoperable NSCLC, RTOG 0324, showed a median survival of 22.7 months and a two-year overall survival rate of 49.3 percent, which are higher than those achieved in past RTOG studies, according to RTOG and the New York City-based ImClone.
“The combination of cetuximab and chemoradiotherapy is well tolerated and shows promise. Further phase III testing in the multicenter setting is warranted,” according to George Blumenschein, MD, the study’s principal investigator from the University of Texas M.D. Anderson Cancer Center in Houston.
Patients entered in the multicenter trial received an initial dose of cetuximab followed by seven weeks of cetuximab, given concurrently with weekly doses of paclitaxel and carboplatin and seven weeks of daily radiotherapy, according to the researchers. The investigators said patients then received cetuximab once a week for three weeks followed by consolidation therapy of six weeks of cetuximab, paclitaxel and carboplatin administered once a week.
RTOG and ImClone reported that adverse events related to the treatment were acceptable with 17 patients experiencing grade IV hematologic toxicity and seven patients with grade III esophagitis.
“We are very excited by these RTOG study results, which show that the addition of cetuximab to chemoradiation produced a considerable improvement in survival compared to previous RTOG studies of various therapeutic regimens in this setting. Additionally, the cetuximab chemoradiation regimen had a similar safety profile to that expected from chemoradiation alone,” said Eric K. Rowinsky, MD, executive vice president and chief medical officer of ImClone. “These data also reinforce the positive data seen with cetuximab in non-small cell lung cancer and can serve as a foundation for further evaluations of cetuximab with chemoradiation in earlier stages.”
“RTOG has long been at the forefront in testing novel agents with radiotherapy,” said Walter J. Curran, Jr., the RTOG group chair, the Lawrence W. Davis professor and chair of the department of radiation oncology in the Emory School of Medicine and chief medical officer of the Emory Winship Cancer Institute. “This trial is another example of RTOG’s commitment to advancing multi-modality cancer research.”
The RTOG investigators are an NCI-funded national cooperative clinical trials group and clinical research enterprise component of the American College of Radiology (ACR).