SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.
Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.
Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.
The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).
"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.
All patients were to receive four cycles of cisplatin 60 mg/m2 on day 1 and capecitabine 625 mg/m2 daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m2 of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m2 weekly.
Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.
Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.
Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.
Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.
Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.