Huimin Fu,1,* Zetan Chen,2,* Jiawei Chen,1 Shuai Zhang1 

1Department of Radiation Oncology, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 2Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiawei Chen; Shuai Zhang, Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19 Xiuhua Road, Xiuying District, Haikou, Hainan Province, 570311, People’s Republic of China, Tel +86 13976658964 ; +86 13876428968, Email chenjiawei9494@163.com; 46370976@qq.com

Purpose: We aimed to determine the safety and feasibility of neoadjuvant immunotherapy combined with sandwich chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC).
Patients and Methods: This retrospective study involved 37 patients with locally advanced NPC treated with the above regimen. All patients received four cycles of neoadjuvant immunotherapy and chemotherapy at three-week intervals, including the administration of PD-1 inhibitors, namely, sintilimab (a fixed dose of 200 mg on Day 1) or toripalimab (240 mg on Day 1). The chemotherapy program consisted of nab-paclitaxel (260 mg/m2, Day 1) plus nedaplatin (85 mg/m2, Day 1). Concurrent with intensity-modulated radiation therapy (IMRT), the patients received targeted drug therapy with nimotuzumab (200 mg) across six cycles. Finally, 4 cycles of S-1 adjuvant chemotherapy were administered.
Results: In this study, the efficiency of neoadjuvant immunotherapy combined with chemotherapy was 94.6%, the CR rate was 67.6%, and the efficiency 3 months after IMRT was 100%. The 2-year overall survival (OS), locoregional control (LCR), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates of the whole group were 97.3%, 94.6%, 97.3% and 91.9%, respectively. Neutropenia was the most common hematological toxicity (100%), and the incidence of grade ≥ 3 neutropenia was 40.5%. Grade 3 anemia and thrombocytopenia did not occur. Additionally, no adverse reactions, such as hypothyroidism, immune pneumonia, or myocarditis, occurred in the whole group. However, the incidences of rash, musculoskeletal pain, and hepatotoxicity were high (45.9%, 54.1% and 37.8%, respectively).
Conclusion: The survival benefit of neoadjuvant immunotherapy combined with sandwich chemoradiotherapy is excellent, with tolerable toxicity, in patients with locally advanced NPC. This study provides new insight into the application of immunotherapy in locally advanced NPC.

Keywords: chemotherapy, immunotherapy, intensity-modulated radiation therapy, nasopharyngeal carcinoma, prognosis