Concurrent chemoradiotherapy plus anlotinib vs. concurrent chemoradiotherapy alone in locally advanced nasopharyngeal carcinoma: An interim analysis of a multicenter randomized controlled trial.

Despite the use of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CCRT), the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is not satisfactory. EGFR and VEGFR are highly expressed in 60-80% of patients with LA-NPC and this is associated with a poor prognosis, which suggests the potential effectiveness of an inhibitor targeting tumor angiogenesis for treating LA-NPC. The present study aimed to assess the safety and effectiveness of CCRT combined with anlotinib in patients with LA-NPC. The study involved patients with LA-NPC (stage III-IVA) from four institutions in Guangxi, China. Patients were randomized to receive CCRT + anlotinib (n=36) or CCRT alone (n=37). Acute toxicity and short-term efficacy were evaluated. The most common grade 3 or 4 adverse events were leucopenia [10 (27.7%) vs. 8 (21.6%)], neutropenia [6 (16.7%) vs. 5 (13.5%)] and mucositis [13 (36.1%) vs. 11 (29.7%)] in the CCRT + anlotinib vs. CCRT cohort but there were no significant differences between the two cohorts (P=0.54, P=0.70 and P=0.56, respectively). Two patients (5.6%) displayed grade 1/2 hemorrhage in the CCRT + anlotinib cohort. No patient displayed grade 3/4 hemorrhages or adverse event-associated deaths in any cohort. Complete response rates in the CCRT + anlotinib arm at 1 week and 3 and 6 months post-radiotherapy were 60.0, 91.4, and 97.1%, respectively, compared with 40.5, 81.1 and 91.9% in the CCRT arm but there was no significant difference (P=0.10, P=0.35 and P=0.65, respectively). This interim analysis of the ongoing trial showed that administration of CCRT + anlotinib has acceptable toxicity profiles, good compliance and promising results in patients with LA-NPC. A larger study cohort and a longer follow-up period are needed to confirm therapeutic effectiveness and late toxicity.