Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.
Department of Oral Pathology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.
Nat Commun. 2022 Sep 14;13(1):5378. doi: 10.1038/s41467-022-33080-8.
Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%-24.3%) and 95% (95% CI: 85.4%-100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC.
新型新辅助治疗方案有望用于口腔鳞状细胞癌（OSCC）。在这项 I 期试验（NCT04393506）中，20 例局部晚期可切除的 OSCC 患者在手术前接受三个周期的卡瑞利珠单抗（200mg，q2w）和阿帕替尼（250mg，每日一次）治疗。主要终点是安全性和主要病理缓解（MPR，定义为≤10%残留存活肿瘤细胞）。次要终点包括 2 年生存率和局部复发率（由于随访不足未报告）。探索性终点是 PD-L1 联合阳性评分（CPS，定义为 PD-L1 染色细胞数除以存活肿瘤细胞总数，再乘以 100）与其他免疫和基因组生物标志物和反应之间的关系。新辅助治疗耐受性良好，MPR 率为 40%（20/20），达到主要终点。CPS＞10 的 5 例患者均达到 MPR。事后分析显示，18 个月的局部区域复发率和生存率分别为 10.5%（95%CI：0%-24.3%）和 95%（95%CI：85.4%-100.0%）。达到 MPR 的患者比未达到 MPR 的患者有更多的 CD4+T 细胞浸润（P=0.02），并且在新辅助治疗后观察到 CD31 和ɑ-SMA 表达水平降低。总之，新辅助卡瑞利珠单抗和阿帕替尼安全且对 OSCC 有很高的 MPR 率。
