Perioperative Camrelizumab Plus Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Randomized Clinical Trial

Importance Despite multimodal treatment, recurrence remains common in patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC). Whether perioperative chemoimmunotherapy improves long-term outcomes remains uncertain. Objective To estimate the effect of perioperative camrelizumab plus chemotherapy on event-free survival (EFS) compared with standard surgery-based treatment in patients with resectable locally advanced HNSCC. Design, Setting, and Participants The CAMORAL trial was a multicenter, phase 2 randomized clinical trial conducted at 4 academic hospitals in China between October 2020 and March 2024, with data cutoff on April 11, 2025. Patients aged 18 to 75 years with untreated, resectable stage III to IVB HNSCC were assigned to neoadjuvant-adjuvant treatment or control. Analyses used the intention-to-treat population. Data were analyzed from May 2025 to February 2026. Interventions Patients were randomized (1:1) to receive two 21-day cycles of neoadjuvant camrelizumab, 200 mg, plus albumin-bound paclitaxel and carboplatin followed by surgery, risk-adapted adjuvant therapy, and maintenance camrelizumab for up to 15 cycles; or upfront surgery followed by standard risk-adapted adjuvant therapy. Main Outcomes and Measures The primary end point was 2-year EFS. Secondary end points included major pathological response (MPR), pathological complete response (pCR), overall survival, 2-year distant metastasis–free survival, 2-year locoregional recurrence–free survival, and safety. Results Of 125 included patients, 99 (79.2%) were male, and the mean (SD) age was 56.3 (11.7) years. A total of 63 patients were assigned to the neoadjuvant-adjuvant group and 62 to the control group; the median (IQR) follow-up was 24.6 (16.8-36.5) months. A total of 103 (82.4%) had oral cavity primary tumors. Among 125 patients, the 2-year EFS rate was 77.8% (95% CI, 63.6-87.0) in the neoadjuvant-adjuvant group compared with 46.1% (95% CI, 31.3-59.6) in the control group (hazard ratio, 0.34; 95% CI, 0.17-0.68; P = .001). MPR and pCR were 47.6% (95% CI, 34.9-60.6) and 25.4% (95% CI, 15.3-37.9), respectively, in the neoadjuvant-adjuvant group, with no MPR or pCR events in the control group. The 2-year overall survival rates were 92.0% and 69.1%, respectively (hazard ratio, 0.25; 95% CI, 0.10-0.64); the hazard ratio of 2-year distant metastasis–free survival was 0.15 (95% CI, 0.03-0.68). Grade 3 or higher treatment-emergent adverse events occurred in 50 of 63 patients (79.4%) in the neoadjuvant-adjuvant group and 35 of 62 patients (56.5%) in the control group; 1 fatal treatment-emergent adverse event occurred in the control group. Conclusions and Relevance In this phase 2 randomized clinical trial, perioperative camrelizumab plus chemotherapy significantly improved EFS with manageable toxic effects, supporting evaluation of intensified perioperative immune priming in resectable HNSCC. Trial Registration ChiCTR.org.cn Identifier: ChiCTR2000037980