Cetuximab (Erbitux) may be an active addition to chemoradiation and chemotherapy for the treatment of locally advanced esophageal cancer, according to the final results of an open-label, single-arm multicenter phase II study conducted in France by the Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR).¹

"The threshold for efficacy was reached," Aimery de Gramont, MD, of the Hospital Saint-Antoine in Paris, announced at the 2011 Gastrointestinal Cancers Symposium, held January 20-22 in San Francisco. The lead investigator of the study was Gerard Lledo, MD, of the Hôpital Privé Jean Mermoz in Lyon.

Dr. de Gramont noted that oxaliplatin has proven superior to cisplatin in esophageal cancer, which is why GERCOR investigators chose FOLFOX (leucovorin, fluorouracil [5‑FU], oxaliplatin) as the chemotherapy backbone, in combination with radiotherapy. Cetuximab was added, based on its demonstrated synergy with both radiotherapy and platinum-based chemotherapy. The ERaFOX trial, therefore, evaluated the safety and efficacy of adding cetuximab to chemoradiotherapy with FOLFOX.

Study Details

The study included 80 patients with untreated stage III squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction. Tumor was located in the esophagus in 74 persons and the cardia in 5.  The treatment was two cycles of FOLFOX induction therapy plus cetuximab, followed by radiotherapy at 50.4 Gy with FOLFOX. Cetuximab, 250 mg/m², was given weekly during induction and during the three cycles of chemoradiotherapy.

Tumors were evaluated after chemoradiotherapy, and the primary endpoint was overall response, with a 50% threshold for efficacy. Complete responses by endoscopic ultrasound and tumor biosies were also assessed.
The intent-to-treat analysis included 79 patients, and the full analysis set included 67 patients. Approximately three-quarters of patients received at least 90% of the planned doses of cetuximab, oxaliplatin, and 5-FU. Approximately 10% of patients received less than 60% of the cetuximab and oxaliplatin doses, whereas just 5% received less than 60% of 5-FU.

Key Results

Responses were observed in 61 patients (77.2%) in the intent-to-treat analysis, which more than met the study's primary endpoint, Dr. de Gramont reported. Six patients (7.6%) had stable disease and only nine (11.4%) showed disease progression while on treatment (three patients were not evaluable). For the full analysis set, the response rate was 80.6%. Complete responses on endoscopic ultrasound were observed in 40% of patients.

The median progression-free survival was 13.8 months, after a median follow-up time of 19.4 months. More than half the population was alive at the time of analysis. Overall survival, postsurgical outcomes, and quality-of-life data are currently being analyzed.

The regimen was fairly well tolerated. The major grade 3/4 toxicities seen with chemoradiotherapy and cetuximab were neutropenia (28%), dysphagia (12%), and rash (11%). One toxic death (1.3%) related to esophagitis with gastrointestinal bleeding occurred after chemoradiotherapy.

"We believe this strategy should be evaluated in a phase III trial," Dr. de Gramont said. ■

Reference

1. Lledo G, Michel P, Dahan L, et al: Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: Final results of a GERCOR phase II trial (ERaFOX). 2011 Gastrointestinal Cancers Symposium. Abstract 8. Presented by Aimery de Gramont, MD, January 20, 2011.