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Top Line: Is radiation alone non-inferior to chemoradiation for low-risk nasopharyngeal cancer?

The Study: Chemoradiation is effective for head and neck cancer, but it’s also toxic. Hence a wave of recent trials attempting to de-escalate therapy for different sub-sites. In the nasopharynx, treatment intensification with additional systemic therapy has proven beneficial for locally advanced NPC. However, there are patients with low risk NPC with excellent treatment outcomes who might benefit from treatment de-intensification. An older randomized, phase 3 trial demonstrated improved overall survival when chemo was added to radiation for early stage NPC. However, more recent studies have questioned the benefit of chemo in early stage disease in the setting of modern radiation therapy. This multicenter randomized phase 3 trial from China sought to determine if radiation alone (RT) provides non-inferior failure-free survival compared to chemoradiation (CRT) for endemic NPC. Eligible patients (n=341) had cT2N0-1 or cT3N0 squamous cell carcinoma of the nasopharynx that was considered low-risk based on the following criteria: all nodes <3cm, no level IV or VB metastases, no ENE, and an EBV DNA titer <4000 copies/mL. Radiation was planned the same in each arm using IMRT with 4 different dose levels including a prescribed dose of 68-70 Gy in 30-33 fractions to the primary. Patients in the chemotherapy arm received 100 mg/m2 cisplatin every 3 weeks for 3 cycles. After 46 months median follow-up, the rate of locoregional failure was 7.6% with RT and 6.5% with CRT, and the rate of distant metastasis was 4.7% v 2.4%. 3-year failure free survival was deemed non-inferior with RT (90.5% v 91.9%). There was no difference in OS between RT and CRT (98.2% v 98.6%). During and after treatment, quality of life outcomes were significantly better with RT. The overall rate of grade 3-4 toxicity with RT alone was less than half that of CRT (17% v 46%). These included lower rates of heme toxicity as well as less vomiting (1% v 15%), weight loss (1% v 5%), and mucositis (10% v 19%). However, there was no difference in late grade 3-4 toxicity.

TBL: At 3 years, RT alone appears to be non-inferior to CRT for definitive treatment of early stage, low-risk, endemic NPC. | Tang, JAMA 2022