Mohan Suntharalingam, MD, MBA
The phase III NRG Oncology RTOG 0436 trial has shown no survival benefit of adding cetuximab (Erbitux) to paclitaxel/cisplatin and radiation therapy in patients with esophageal cancer treated without surgery. These results were reported by Mohan Suntharalingam, MD, MBA, of the Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, and colleagues in JAMA Oncology.
In the trial, 328 evaluable patients were randomized between June 2008 and February 2013 to receive weekly concurrent cisplatin at 50 mg/m2, paclitaxel at 25 mg/m2, and daily radiation at 50.4 Gy/1.8 Gy fractions with (n = 159) or without (n = 169) weekly cetuximab consisting of 400 mg/m2 on day 1 followed by 250 mg/m2 weekly. The primary endpoint was overall survival. Overall, 80% of patients had T3 or T4 disease, 66% had N1 disease, 19% had celiac nodal involvement.
Overall Survival and Toxicity
Median follow-up was 18.6 months. Overall survival rates for the cetuximab vs control groups were 45% vs 44% at 24 months and 34% vs 28% at 36 months (hazard ratio [HR] = 0.90, P = .47). Local failure rates were 47% vs 49% at 24 months and 49% vs 49% at 36 months (HR = 0.92, P = .65). Complete clinical response rates were 56% vs 58%, with no differences observed according to adenocarcinoma or squamous cell histology.
The rates of grade 3, 4, and 5 treatment-related adverse events in the cetuximab vs control groups were 46% vs 50%, 23% vs 17%, and 4% vs 1%, respectively. Grade ≥ 3 hematologic toxicity occurred in 45% vs 44%, and grade ≥ 3 gastrointestinal toxicity occurred in 44% vs 36%.
The investigators concluded: “The addition of cetuximab to concurrent chemoradiation did not improve [overall survival]. These phase 3 trial results point to little benefit to current [epidermal growth factor receptor]–targeted agents in an unselected patient population and highlight the need for predictive biomarkers in the treatment of esophageal cancer.” ■