The combination of radiation therapy plus cetuximab had higher rates of acute toxicity among patients with locally advanced squamous cell carcinoma of the head and neck compared with radiation therapy plus cisplatin.
The combination of radiation therapy plus the EGFR inhibitor cetuximab had higher rates of acute toxicity among patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) compared with radiation therapy plus the chemotherapy cisplatin, according to results of a phase II trial based in Italy. Efficacy was similar with both combination therapies.
According to Stefano Maria Magrini, MD, professor of radiotherapy at the UniversitÃ degli Studi di Brescia in Italy, and colleagues, this is the first clinical trial to directly compare radiation therapy plus cetuximab to a chemoradiation regimen for SCCHN.
The results of the randomized trial are published in the Journal of Clinical Oncology.
Cetuximab was approved in combination with radiation therapy by the US Food and Drug Administration in 2006 for the treatment of unresectable SCCHN.
Despite a goal of recruiting 130 patients, only 70 patients were recruited between 2011 and 2014.
The 1- and 2-year overall survival rates were 75% and 68% in the cetuximab arm compared with 78% in the cisplatin arm. The 1- and 2-year local control rates were 64% and 53% in the cetuximab arm and 84% and 80% in the cisplatin arm, yet the differences between arms were not statistically significant (P = .073), reflecting the inadequate statistical power of the relatively small trial.
Compliance in both treatment arms was relatively low. Only 28% of patients in the cetuximab arm and 20% of patients in the cisplatin arm received at least 7 cycles of therapy.
Patients in the radiation therapy plus cetuximab arm experienced more serious adverse events including severe cutaneous toxicity of grade 3 or higher. Four patients in the cetuximab arm developed infectious complications that led to septic shock and three of the patients died after the end of treatment. An additional patient died from respiratory failure caused by aspiration pneumonia.
Patients in the cisplatin arm had more frequent hematologic toxicities compared to patients in the cetuximab arm and one patient died from adverse events possibly related to treatment.
“The incidence of both the infusion reactions and of the other severe adverse events does not allow to consider cetuximab a safer and easy-to-use alternative to standard chemotherapy regimens,” wrote the study authors.
Based on the study results, larger prospective trials are needed to understand which SCCNH patients would best benefit from radiation therapy plus cetuximab regimen.
In an accompanying editorial, Roy H. Decker, MD, PhD, associate professor of therapeutic radiology at the Yale School of Medicine in New Haven, Connecticut, and colleagues highlighted the limitations of the current trial but look forward to results from ongoing studies to clarify the role of cetuximab in the treatment of SCCHN.
“We continue to selectively consider the use of cetuximab-based radiation therapy in patients with otherwise-favorable, low-risk disease-p16-positive, T1–T3 N0–N2b with a smoking history of less than 10 pack-years,” wrote the editorial authors.