Prospective Efficacy of Two Cycles Toripalimab Plus Induction Chemotherapy in T4 or N3 Locoregionally Advanced Nasopharyngeal Carcinoma: A Retrospective and Mechanistic Study

Abstract

Gemcitabine-cisplatin (GP) as the most commonly used induction chemotherapy is the standard first-line systemic treatment for advanced nasopharyngeal carcinoma. However, the toxicity of three cycles induction chemotherapy following on chemoradiotherapy remains a pertinent issue. Additional monoclonal antibody against human programmed death-1 (PD-1) has shown promising efficacy in recurrent or metastatic nasopharyngeal carcinoma. In this study, we compared three cycles of gemcitabine and cisplatin as classical induction chemotherapy with two cycles of induction chemotherapy plus toripalimab, and then both groups treated with the similar concurrent chemoradiotherapy. Patients with locoregionally advanced nasopharyngeal carcinoma staging T4 or N3 were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1-3), administered every 3 weeks for three cycles, or GP combined with toripalimab (at a dose of 240mg) for two cycles. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. A total of 60 patients were included in the trial (30 patients in the toripalimab combined induction chemotherapy group and another 30 in the standard-therapy group). Among 60 patients evaluable for response assessment after induction therapy, all patients had overall response in combined group, including 10 patients (30%) with complete response (CR) in the primary tumor site. 21 patients (70%) were evaluated as partial response (PR) in the standard induction chemotherapy, and another 9 patients were assessed as SDa. At a median follow-up of 27.6 months, the 6-months, 1-, 2-year recurrence-free survival was 100% vs 86.7%, 100% vs 80%, 93% vs 70% in the toripalimab combined induction chemotherapy group and standard-therapy group (stratified hazard ratio for recurrence or death, 0.62; 95% confidence interval [CI], 0.38 to 0.87; P = 0.001). Overall survival at 2 years was 93.3% and 100%, respectively (stratified hazard ratio for death, 0.53; 95% CI, 0.29 to 0.79). The incidence of acute adverse events of grade 3 or 4 was 76.8% in the standard-induction chemotherapy group and 56% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 10.2% in the induction chemotherapy group and 10.4% in the combined-therapy group. Two cycles of toripalimab combined with induction chemotherapy of and CCRT shows excellent distant metastatic control with acceptable safety, which is a new promising and effective systemic therapy regimen for high-risk of metastatic NPC patients.