The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer has been increasing. The standard cisplatin-based chemoradiotherapy treatment for HPV-positive oropharyngeal cancer is associated with significant acute and long-term toxicity. Cetuximab, an epidermal growth factor inhibitor, is thought to have lower toxicity and therefore may be a good alternative treatment option.
However, results of an open-label, randomized, controlled phase 3 trial, published in The Lancet, has shown that although cetuximab-based treatment has similar toxicity rates as cisplatin-based chemoradiotherapy, surprisingly, overall survival rates were poorer among those treated with cetuximab.
Researchers recruited a total of 334 patients aged 18 years or older with low-risk HPV-positive oropharyngeal cancer from 32 head and neck treatment centers in Ireland, the Netherlands, and the United Kingdom between November 2012 and October 2016. Patients were randomized to cisplatin 100 mg/m2IV (166 patients) or cetuximab 400 mg/m2IV (168 patients), plus radiation therapy.
At 24 months, no significant difference was seen in overall (acute and late) severe (grades 3 to 5) toxicity between the 2 groups, and no significant difference was seen in the overall all-grade toxicity. However, a significant difference was noted in the overall 2-year survival (97.5% for cisplatin vs 89.4% for cetuximab) and 2-year recurrence (6% for cisplatin vs 16.1% for cetuximab).
The study authors recommend that cisplatin and radiation therapy remain the primary standard of care for low-risk HPV-positive patients. “Our findings also suggest caution with de-escalation strategies and highlight the importance of phase 3 trial data before changing clinical practice,” the authors wrote.
Mehanna H, Robinson M, HartleyA, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.Lancet. 2019;393(10166):51-60.