Abstract:

Objective To analyze the clinical efficacy and safety of full-course toripalimab combined with induction chemotherapy and concurrent chemoradiotherapy （CCRT） in the treatment of locally advanced nasopharyngeal carcinoma （LANPC）. Methods A total of 96 patients with initially diagnosed LANPC admitted to the Second Affiliated Hospital of Guangxi University of Science and Technology and People's Hospital of Laibin，Guangxi Zhuang Autonomous Region from January 2021 to December 2023 were enrolled. Patients were divided into the immunotherapy group （n=47） and the control group （n=49） based on whether they received immunotherapy. The control group received induction chemotherapy with the GP regimen （gemcitabine+cisplatin） and CCRT，the immunotherapy group received the same regimen as the control group，along with the addition of toripalimab immunotherapy throughout the treatment process. The therapeutic effects of the two groups of patients were compared. Kaplan-Meier survival curves were plotted to evaluate the survival status of the patients，the 2-year failure-free survival （FFS） rate，2-year overall survival （OS） rate，2-year distant metastasis-free survival （DMFS） rate and 2-year locoregional relapse-free survival （LRFS） rate were compared using the log-rank test. The influencing factors of patients' FFS were analyzed using Cox proportional hazards regression model. Adverse events were compared between the two groups. Results By the follow-up deadline，13 patients died，including 6 （12.77%） in the immunotherapy group （1 due to immune-related pneumonitis with infection，5 due to progression or metastasis of nasopharyngeal carcinoma） and 7 （14.28%） in the control group （all due to progression or metastasis of nasopharyngeal carcinoma）. At 3 months after treatment，there were 36 cases of complete response （CR），10 cases of partial response （PR），and 1 case of stable disease （SD） in the immunotherapy group； and 37 cases of CR，10 cases of PR，and 2 cases of SD in the control group. The objective response rate was 97.87% （46/47） in the immunotherapy group and 95.92% （47/49） in the control group，the disease control rates of the two groups were 100% （47/47） and 100% （49/49） respectively，with no statistically significant differences （χ²=0.30，P=0.582； P>0.999）. The 2-year FFS rates of the immunotherapy group and the control group were 85.10% and 67.34% respectively，with a statistically significant difference （χ²=4.23，P=0.040）. The 2-year OS rates were 97.87% and 93.87% respectively，with no statistically significant difference （χ²=1.10，P=0.294）. The 2-year DMFS rates were 89.36% and 79.59% respectively，with no statistically significant difference （χ²=2.00，P=0.158）. The 2-year LRFS rates were 95.74% and 87.75% respectively，with no statistically significant difference （χ²=2.41，P=0.121）. Multivariate analysis showed that，combined immunotherapy，age，gender，pathological type，T stage，N stage，American Joint Committee on Cancer stage，radiation duration, EBV-DNA level，and EBV antibodies were not independent influencing factors of FFS in patients （all P>0.05）. There were no statistically significant differences between the two groups in the incidence of leukopenia，neutropenia，thrombocytopenia，anemia，pneumonia，hypothyroidism，fever，fatigue，weight loss，or gastrointestinal system reactions （all P>0.05）. Conclusions The full-course toripalimab combined with induction chemotherapy and CCRT，although does not significantly improve the short-term efficacy，2-year OS rate，DMFS rate，or LRFS rate of patients with LANPC，it can increase the 2-year FFS rate，and not increase adverse reactions.

Key words: Nasopharyngeal neoplasms, Chemoradiotherapy, Immunotherapy, Treatment outcome, Drug-related side effects and adverse reactions