In a phase II trial (Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group E3205) reported in the Journal of Clinical Oncology, Garg et al found that the addition of cetuximab (Erbitux) to definitive chemoradiotherapy appeared to reduce the rates of locoregional failure but increase the risk of severe toxicity in patients with squamous cell carcinoma of the anal canal. Joseph A. Sparano, MD, of Montefiore Einstein Center for Cancer Care, is the corresponding author of the Journal of Clinical Oncology article.
The study involved 61 patients with stage I to III squamous cell carcinoma of the anal canal receiving sphincter-preserving definitive chemoradiotherapy. Chemoradiotherapy included cisplatin, fluorouracil (5-FU), and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy), with cetuximab added as 8 once-weekly concurrent doses. The study was designed to detect a reduction of ≥ 50% in the 3-year locoregional failure rate, assuming a rate of 35% from historical data.
Overall, 64% of patients had stage III disease, and tumors were human papillomavirus (HPV)-positive in 25 of 28 specimens (89%) evaluated. The first 28 patients enrolled received 2 cycles of neoadjuvant cisplatin/5-FU, with the remaining patients not receiving neoadjuvant treatment.
Outcomes and Toxicity
Among all patients, the 3-year locoregional failure rate was 23% (95% confidence interval [CI] = 13%–36%, P = .03). Three-year rates were 68% (95% CI = 55%–79%) for progression-free survival and 83% (95% CI = 71%–91%) for overall survival. Objective response rates were 63% and 65% among patients receiving and not receiving neoadjuvant treatment. respectively.
The most common grade 3 and 4 adverse events in patients not receiving neoadjuvant therapy were diarrhea (68% grade 3, 0% grade 4), neutropenia (26% grade 3, 24% grade 4), nausea (32% grade 3, 0% grade 4), and dehydration (32% grade 3, 0% grade 4); adverse events were similar in patients receiving neoadjuvant therapy, except for a lower incidence of grade 3 or 4 neutropenia (24%). Overall, grade 4 toxicity occurred in 32% of patients, and treatment-related death occurred in 5%.
The investigators concluded: “Although the addition of cetuximab to chemoradiation for [squamous cell carcinoma of the anal canal] was associated with lower [locoregional failure] rates than historical data with [chemoradiotherapy] alone, toxicity was substantial, and [locoregional failure] still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.”
The study was supported by Public Health Service grants, the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services.