Tislelizumab plus gemcitabine–cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for high-risk locally advanced nasopharyngeal carcinoma in a non-endemic region of China: a prospective single-center pilot phase II study

To evaluate the feasibility, safety, and preliminary antitumor activity of tislelizumab plus gemcitabine–cisplatin induction chemotherapy followed by concurrent chemoradiotherapy in patients with high-risk locally advanced nasopharyngeal carcinoma from a non-endemic region of China. This prospective, single-center study enrolled patients with pathologically confirmed, previously untreated, high-risk, non-metastatic nasopharyngeal carcinoma, classified as T 4 N 0–3 M 0 or T 1–4 N 3 M 0 according to the American Joint Committee on Cancer, 8th edition. Treatment was administered at the Second People’s Hospital of Neijiang between January 2022 and December 2023. All patients received three cycles of tislelizumab plus gemcitabine–cisplatin induction chemotherapy followed by concurrent chemoradiotherapy. Tumor response and adverse events were assessed using standard response and toxicity criteria. Survival outcomes were estimated using the Kaplan–Meier method. The primary endpoint was event-free survival. Secondary endpoints included complete response rate, overall survival, distant metastasis-free survival, locoregional recurrence-free survival, and safety. Twenty-two patients were enrolled. One patient withdrew before treatment initiation because of rapid disease progression and renal dysfunction and did not receive study treatment. Therefore, 21 patients were included in the treated and safety populations. After induction therapy, the objective response rate was 95.2% for primary nasopharyngeal lesions, including 33.3% complete responses and 61.9% partial responses, and 100.0% for cervical lymph nodes, including 23.8% complete responses and 76.2% partial responses. After concurrent chemoradiotherapy, the complete response rate was 100.0% for primary lesions and 95.2% for cervical lymph nodes. With a median follow-up of 37.9 months, the 36-month event-free survival rate was 80.0%; 10 patients remained at risk at the 36-month landmark. The 36-month locoregional recurrence-free, distant metastasis-free, and overall survival rates were 90.5%, 94.4%, and 95.2%, respectively. The most common toxicities were hematologic events, gastrointestinal toxicities, and radiotherapy-related oral mucositis and dermatitis. No treatment discontinuations occurred because of immune-related adverse events. In this exploratory pilot study, induction-phase tislelizumab plus gemcitabine–cisplatin followed by concurrent chemoradiotherapy was feasible and showed preliminary tumor-control activity in patients with high-risk locally advanced nasopharyngeal carcinoma from a non-endemic region of China. Future large-scale prospective randomized controlled trials are warranted to evaluate the value of this strategy in non-endemic populations. Chinese Clinical Trial Registry, ChiCTR2300078941, registered on 21 December 2023, retrospectively registered.