Use of the EGFR inhibitor cetuximab with chemoradiation did not improve survival in patients with esophageal carcinoma compared with chemoradiation alone, according to the results of the phase III RTOG 0436 trial.
Use of the epidermal growth factor receptor (EGFR) inhibitor cetuximab with chemoradiation did not improve overall survival (OS) in patients with esophageal carcinoma compared with chemoradiation alone, according to the results of the phase III RTOG 0436 trial.
“The results of the NRG Oncology RTOG 0436 trial are consistent with other phase III studies that have failed to demonstrate OS improvements with the addition of EGFR inhibition to concurrent chemoradiation regimens for various solid tumors,” wrote Mohan Suntharalingam, MD, MBA, of the University of Maryland School of Medicine and colleagues in a study published in Lancet Oncology. “Taken together, these trial results highlight the need to identify prognostic variables that may provide insight into which patient populations will benefit from EGFR inhibition.”
The standard of care for patients with non-operable esophageal cancer is a combination of cisplatin, 5-fluorouracil, and radiotherapy. Preclinical models had suggested a synergy between EGFR inhibitors-targeting EGFR overexpression, which is present in 50% of esophageal cancers-chemotherapy, and radiation. Therefore, with this trial, the researchers enrolled 344 patients with biopsy-proven carcinoma and randomly assigned them to weekly concurrent cisplatin, paclitaxel, and daily radiation with or without weekly cetuximab.
An early planned interim analysis of the first 150 patients with adenocarcinoma showed no significant improvement in complete response with the addition of cetuximab, and the trial stopped enrolling patients with adenocarcinoma. Later, accrual to the trial was stopped when results of a similar trial showed no benefit with the addition of cetuximab to chemoradiation. Follow-up has continued to report outcomes for patients who had already been enrolled.
There was no significant difference in the clinical response rate between the cetuximab and the control arms (56% vs 58%). This lack of difference was consistent for patients with adenocarcinoma or squamous cell carcinoma.
With a median follow-up of 18.6 months, patients in the cetuximab arm had a 24-month local failure rate of 47% and a 36-month local failure rate of 49% compared with 49% and 49%, respectively, for patients in the control arm.
Finally, there were no significant differences between the two arms for OS. The median OS was 19.7 months for cetuximab compared with 19 months for the control arm. In the cetuximab arm, the 24-month OS was 45% and the 36-month OS was 34% compared with 44% and 28% in the control arm.
“It is important to note that this trial was specifically designed to test the addition of cetuximab in the nonoperative setting,” the researchers wrote. “Given that consensus does not exist regarding the use of trimodality therapy, this study included patients who were deemed to be medically unfit for surgery as well as those whose treating physicians supported a nonoperative approach.”