WCLC: Cetuximab May Improve Survival in Some Patients With EGFR-Positive Squamous NSCLC
Analysis of a large phase III trial (S0819) suggested that adding the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody cetuximab (Erbitux) to chemotherapy benefits survival in patients with squamous cell non–small cell lung cancer (NSCLC) with tumors positive for EGFR gene copy number (fluorescent in situ hybridization). No survival advantage was found among patients with nonsquamous histology and those with EGFR fluorescent in situ hybridization–negative tumors. These findings (PLEN4.01) were presented at the 16th World Conference on Lung Cancer (WCLC) in Denver, Colorado. This Conference was hosted by the International Association of the Study of Lung Cancer.
Roy Herbst, MD, PhD, Ensign Professor of Medicine, Professor of Pharmacology, Chief of Medical Oncology, Director of the Thoracic Oncology Research Program, and Associate Director for Translational Research at the Yale Comprehensive Cancer Center and Yale School of Medicine, presented the research on behalf of SWOG, a National Cancer Institute–funded national group, and the National Clinical Trials Network (NCTN).
Previous research demonstrated that cetuximab moderately increases survival in patients with advanced NSCLC.
“Our prior work suggested that EGFR gene copy number measured by fluorescent in situ hybridization (FISH) could identify those patients most likely to benefit from adding cetuximab,” Dr. Herbst said.
Study Details and Findings
Patients eligible for this phase III trial had newly diagnosed stage IV NSCLC. Patients with controlled brain metastases were allowed entry. The study required all patients to have tumor tissue available for molecular testing, including EGFR FISH, which was a coprimary endpoint of the trial. Randomization was stratified by the appropriateness for bevacizumab (Avastin) treatment, smoking status, and M substage. The coprimary objectives were progression-free survival in EGFR-FISH–positive patients and overall survival in the overall study population. Secondary objectives were overall survival in FISH-positive patients and clinical outcomes (progression-free survival and overall survival) comparison among bevacizumab-appropriate and -inappropriate patients.
Researchers enrolled 1,313 patients in the trial. Dr. Herbst and his team found that while there was no significant difference in the overall study population’s survival rate, data indicated some increase in survival in the FISH-positive group, regardless of histology, although the benefit was not statistically significant. However, the study found a significant increase in survival in the FISH-positive group that did not receive bevacizumab, and this was especially pronounced in those with squamous cell carcinoma.
“Squamous cell carcinoma is a minority subtype of lung cancer for which we have seen few new targeted therapies in the last 20 years. These data are hypothesis generating, suggesting that EGFR FISH is a potential biomarker than can be used for study of cetuximab or similar drugs in the future,” Dr. Herbst said. “These data support using this biomarker for determining who should receive an EGFR antibody inhibitor with chemotherapy, within the squamous subgroup.”
Support for S0819
“These EGFR FISH results, when taken together with the biomarker results from the SQUIRE trial presented here at WCLC, which are strikingly similar, suggest that we can identify a population of patients most likely to benefit from this combination therapy, and that the survival impact in this population will be substantial. It is now up to lung cancer researchers to validate these results. S0819 also shows the power of NCI-NCTN to conduct a prospective biomarker-driven trial in lung cancer, with S0819 being the first of this type. Patients were enrolled from a large number of institutions from across the country, including a majority from community centers. More and more, the goal is to ‘take the trial to the patient,’ in whatever community they reside, rather than making the patient travel to one of a few centers, which may be hundreds of miles away. In this regard, these NCTN trials are truly transformative,” said David R. Gandara, MD, Professor of Medicine in the Division of Hematology/Oncology; Director of the Thoracic Oncology Program; Senior Advisor to the Director at the University of California Davis Comprehensive Cancer Center; and Chair of the SWOG Lung Cancer Committee.
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