Toripalimab plus anlotinib in patients with recurrent or metastatic nasopharyngeal carcinoma: A multicenter, single-arm phase 2 trial (TORAL).

Treatment options for patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) after failure of platinum-based therapy are limited. In this phase 2 trial, 40 patients with RM-NPC who failed platinum-based chemotherapy receive toripalimab plus anlotinib regimen. The objective response rate is 37.5%, and the disease control rate is 85.0%. With a median follow-up of 17.4 months, the median progression-free survival (PFS) is 9.5 months and 1-year overall survival rate is 73.3%. The most common treatment-related grade 3-4 adverse events are hand-foot syndrome (22.5%) and oral mucositis (17.5%). Analyses of plasma circulating tumor DNA (ctDNA) demonstrate that the blood tumor mutation burden at cycle 1/2 is associated with response and PFS, and disease progression indicated by ctDNA precedes radiological progression by a median of 2.3 months. In conclusion, toripalimab plus anlotinib is well tolerated and shows promising efficacy in patients with RM-NPC, and ctDNA could be a potential predictive biomarker. The trial is registered at ClinicalTrials.gov (NCT04996758).