Neoadjuvant PD-1 inhibitor combined with Nab-paclitaxel and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NCT05522985): A randomized, controlled, open label, phase II clinical trial.

Abstract

6018 Background: More than 60% of head and neck squamous cell carcinoma (HNSCC) patients (pts) were locally advanced at diagnosis. Many previous clinical trials have confirmed that induction chemotherapy can improve the functional retention rate of HNSCC and improve the quality of life. However, pts have no long-term survival benefits from it. In recent years, immunotherapy has brought hope for long-term survival to pts with recurrent and metastatic HNSCC. The exploration of neoadjuvant immunotherapy in HNSCC is also gradually carried out. Methods: This was a randomized, controlled, open label, phase II study. 122 pts were panned to enrolled. Key inclusion criteria: pts aged ≥18 years; histologically or cytologically confirmed stage III or IV resectable HNSCC; without prior system anticancer therapy; ECOG≤1. Eligible pts were randomized 1:1 to receive toripalimab (240mg, D1, q3w) in combination with nab-paclitaxel (260 mg/m2,d1,q3w) and cisplatin (75mg/m 2 ,q3w) for 3 cycles (experimental arm) or nab-paclitaxel (260 mg/m 2 ,d1,q3w) and cisplatin (75mg/m 2 , q3w) for 3 cycles (control arm). Then surgery and pathological remission evaluation was performed. The primary endpoint was pathologic complete response (pCR) rate. Secondary endpoints were major pathological response (MPR), objective response rate (ORR), 2-year progression-free survival (PFS) rate, 2-year overall survival (OS) rate, and safety. Results: A total of 122 pts were enrolled (experimental 61, control 61). Median age was 59.5 years (range: 34–83) and 80.33% were male. After neoadjuvant treatment, 88 pts underwent surgery (experimental 45, control 43). pCR rate was significantly different between the two arms (experimental 57.78%, control 34.88%, p = 0.03). More pts achieved MPR (experimental 82.22%, control 53.46%, p = 0.004) in experimental arm. In experimental arm, 2-year DFS (experimental 86.67%, control 71.95%) and 2-year OS (experimental 90.61%, control 77.74%) were higher, the statistical significance was undetermined. The proportion of Grade ≥3 treatment-related adverse events (TRAEs) in the experimental and control arms were 16.39% and 9.84%, respectively. The most common TRAEs are Agranulocytosis, Nausea, Alopecia and Vomiting. No new safety signals were observed and no TRAEs leading to death. There was no significant difference in TRAEs of two arms. Conclusions: Comparing to chemotherapy, neoadjuvant immunochemotherapy can significantly improve the pCR and MPR rate of HNSCC. Moreover, adverse events are controllable. And immune neoadjuvant therapy demonstrates a trend towards improving survival. Clinical trial information: NCT05522985 .