Cetuximab Reduces Locoregional Failure in Anal Canal Carcinoma, Adds Toxicity

Adding cetuximab to chemoradiation (CRT) yielded better locoregional failure (LRF) rates than historical data in a small trial of patients with squamous cell carcinoma of the anal canal, but the treatment resulted in substantial toxicity.

Squamous cell carcinoma of the anal canal is a relatively rare cancer that is potentially curable with sphincter-sparing definitive chemoradiation. LRF occurs in as many as one third of patients, however. “New approaches are needed to develop more effective therapies that result in improved local and systemic disease control,” wrote study authors led by Joseph A. Sparano, MD, of Montefiore Medical Center in New York. Cetuximab enhances radiation therapy’s effect in human papilloma virus (HPV)-associated oropharyngeal cancer, so researchers hypothesized that it might reduce LRF in squamous cell carcinoma of the anal canal.

The new study included 61 patients with stage I–III squamous cell carcinoma of the anal canal; patients received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and to regional lymph nodes, along with eight once-weekly doses of cetuximab. The first 28 patients were treated with neoadjuvant chemotherapy (arm A), and the other 33 were not (arm B). The results were published online ahead of print in the Journal of Clinical Oncology.

At 3 years, nine patients (15%) had a locoregional recurrence; another seven patients (11%) died without locoregional recurrence (two from disease or treatment within 3 years, and five from other or unknown causes). The remaining 45 patients (74%) did not have an LRF event. The 3-year LRF rate was 23%.

There was an objective response rate of 65%, and this was similar in arm A (63%) and arm B (67%). There were more complete responses in arm A than arm B (59% vs 35%). The 3-year progression-free survival rate was 68%, and the 3-year overall survival rate was 83%. The authors noted that clinical outcomes were less favorable in arm B compared with arm B, but that was likely due to a change in eligibility criteria that allowed for higher-risk disease.

There was significant toxicity with the therapy. The most common grade 3/4 adverse events included diarrhea, neutropenia, nausea, dehydration, and others. There were three deaths within 30 days of treatment completion, and one of those was deemed possibly related to treatment (arm B, renal failure and pneumonitis).

“Although these findings suggest that the addition of cetuximab to CRT for anal cancer may reduce LRF rates, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies,” the authors concluded.

In an accompanying editorial led by Rob Glynne-Jones, MD, of Mount Vernon Hospital in the United Kingdom, experts noted that future trials should be designed for patients with both HPV-positive and HPV-negative disease, and should be stratified according to smoking status and disease staging. “Successful validation of these approaches will allow more effective selection of individualized treatment of patients, in both the context of routine care and clinical trials,” they wrote.