Cetuximab Plus RT Benefits Some with Head and Neck Cancer

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online on January 22 in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.