Research presented at the 2014 Gastrointestinal Cancers Symposium that involved collaborations among the University of Maryland Marlene and Stewart Greenebaum Cancer Center, Texas Oncology, the University of Texas MD Anderson Cancer Center, and other institutions suggests that adding cetuximab to chemoradiation treatment of esophageal carcinoma provides no additional benefit to patients’ overall survival. Mohan Suntharalingam, M.D., professor of radiation oncology at the University of Maryland School of Medicine, explained the findings of the randomized Phase III trial RTOG 0436 that evaluated 328 eligible patients with biopsy-proven squamous cell or adenocarcinoma of the esophagus who were undergoing chemoradiation treatment with or without weekly cetuximab, which is an epidermal growth factor receptor (EGFR) inhibitor.
The study’s goal was to see an increase in two-year overall survival from 41% to 53% because “a survival advantage has been shown with concurrent chemotherapy and radiation,” said Dr. Suntharalingam. Study discussant Manish Shah, M.D., from Weill Cornell Medical College in New York City, called the study well designed and executed, giving the findings credibility in esophageal cancer research. Enrolled patients were stratified by histology, tumor size, and celiac lymph node involvement.
Similar to other studies, RTOG 0436 reported that yet another EGFR inhibitor fails to improve patient survival. After one year of the study, overall survival of the +cetuximab group was 64% vs. 65% in the -cetuximab group, and when the study was completed a year later, the overall survival was still similar: +cetuximab had an overall survival of 44% vs. 42% in -cetuximab (p=0.70 for both time points). Moreover, the tumors appeared histologically no different between the two groups. Finally, the complete clinical response was no different between the two groups (56% vs. 59%, p=0.72) or between squamous cell carcinoma and adenocarcinoma.
Adverse events were similar between groups, but dermatologic events were higher in the cetuximab group. This is consistent with the unrelated Phase II/III SCOPE 1 trial that evaluated cetuximab with chemoradiotherapy in localized esophageal cancer. SCOPE 1 was ended early when the cetuximab-receiving patients experienced significantly higher rates of grade 3 or 4 nonhematologic toxicities due to increases in cardiac, dermatologic, and metabolic toxicities.
A scientist’s work is never done. Dr. Shah recommends that ongoing trials be conducted to improve response to therapy, optimize targeted therapy, and improve the understanding of tumor biology. For now, Dr. Suntharalingam states, “We had the opportunity to look at patients’ endoscopic response 6 to 8 weeks after the completion of therapy. What we found was that patients who achieved a clinical response at 6 to 8 weeks had an improved overall survival. This held for both adenocarcinoma and squamous cell carcinoma. So we found that endoscopic response at 6 to 8 weeks was predictive of overall survival.”
The study was supported by RTOG CA21661 and CCOP CA3742 NCI grants and by Bristol-Myers Squibb. The authors have disclosed no relevant financial relationships.