The E1308 Trial: Reduced-Dose IMRT in HPV-Associated OPSCC After Induction Chemotherapy
In the E2399 trial, HPV+ patients with oropharyngeal squamous cell carcinoma (OPSCC) attained 2-year overall survival (OS) of 95% and progression-free survival (PFS) of 86% when treated with induction chemotherapy (IC) and 70 Gy chemoradiation. The current E1308 trial examined whether intensity- modulated radiation therapy (IMRT; 54 Gy, which represents a 23% dose reduction) could maintain high locoregional control in patients with OPSCC who had a clinical complete response (cCR) to IC (Cmelak A, et al. ASCO 2014. Abstract LBA6006). In this trial, 90 patients with resectable stage III/IVA-B, HPV+ OPSCC received IC with paclitaxel, cisplatin, and cetuximab. The IC response determined the IMRT dose—IMRT 54 Gy if the patients achieved a cCR, and 69.3 Gy if they achieved less than a cCR. After IC, 71% of the patients achieved a cCR. At 23 months, 84% of all reduced-dose IMRT patients exhibited PFS, 94% had locoregional control, and 24-month OS was 95%. Lower PFS rates were observed in patients with T4A and N2C tumor and nodal stage (69%-77%) and in those who had been a >10-pack-year smoker (71%). In contrast, 64% of standard-dose radiation therapy patients exhibited a 23-month PFS, and OS at 24 months was 87%. Thus, IC plus reduced-dose cetuximab-IMRT appears to be a candidate for standard therapy in this patient population.