局部晚期头颈鳞状细胞癌诱导免疫治疗联合化疗探索研究

Exploratory study on induction immunotherapy combined with chemotherapy for locally advanced head and neck squamouscarcinoma

目的 探讨局部晚期头颈鳞状细胞癌(head and neck squamous carcinoma,HNSCC)应用程序性细胞死亡蛋白-1(programmed death-1,PD-1)抑制剂诱导免疫治疗联合化疗的近期疗效及安全性。方法 选择2020年5月-2022年5月济宁医学院附属医院肿瘤科初诊不可手术切除的局部晚期HNSCC患者25例,所有患者接受PD-1抑制剂诱导免疫治疗联合化疗3个周期,具体用法:PD-1抑制剂200 mg,每3周为1个周期,化疗方案为铂类联合紫杉类化疗药物(不适合铂类或紫杉类患者调整为氟尿嘧啶、吉西他滨)。3个周期诱导化疗后采用实体瘤疗效评价标准(RECIST1.1)评估近期疗效,根据PD-L1表达分层分析每亚组疗效分析,另外对治疗相关不良反应进行分析。结果 25例患者中疗效评价部分缓解(PR)21例(84%),其中肿瘤体积缩小≥50%为15例(60%),客观缓解率(ORR)为84%,疾病控制率(DCR)为88%。16例患者进行了联合阳性分数(combined positive score,CPS)检测评估PD-L1表达情况,CPS≥5占50.0%(8/16),其中CPS≥20占25.0%(4/16),另外9例患者未能行CPS检测而PD-L1表达不明。根据PD-L1表达分层分析来看,5≤CPS<20和CPS≥20的患者,肿瘤体积缩小均≥50%,ORR为100%,而CPS<5的所有患者中1例PR肿瘤体积缩小≥50%,PD为2例,ORR为62.5%(5/8)。最常见的不良反应为恶心、白细胞减少和贫血。3例患者出现甲功异常,1例肾功能损害,2例肝功能损害,2例肺炎患者。无3-4级不良反应。结论 局部晚期HNSCC,尤其IVA/IVB期患者,诱导免疫治疗(PD-1抑制剂)联合化疗近期疗效明显,对于CPS≥5的患者疗效更显著,无严重毒副反应发生,有望成为局部晚期头颈部鳞癌新的治疗模式。

OBJECTIVE To investigate the short term efficacy and safety of programmed death-1(PD-1)inhibitorinduced immunotherapy combined with chemotherapy for locally advanced head and neck squamous cell carcinoma(HNSCC).METHODS Twenty-five patients with non-surgically resectable,locally advanced HNSCC from May 2020 to May 2022 who were initially diagnosed in the Department of Oncology of the Affiliated Hospital of Jining Medical College were selected to receive 3 cycles of PD-1 inhibitor immunotherapy combined with induction chemotherapy,as follows:PD-1 inhibitor 200 mg every 3 weeks,chemotherapy regimen of platinum combined with paclitaxel chemotherapy drugs.After 3 cycles of induction chemotherapy,the short term efficacy was evaluated using RECIST1.1.The short term efficacy was also analyzed in every subgroup according to the stratified PD-L1 expression,and the treatment-related adverse effects were also recorded.RESULTS Among the 25 patients,21 patients(84%)achieved PR,15 patients(60%)achieved large PR(≥50%tumor volume reduction),ORR was 84%,and DCR was 88%.The CPS(Combined Positive Score)test was performed in 16 patients to assess PD-L1 expression,with CPS≥5 in 50.0%and CPS≥20 in 25.0%.The other 9 patients failed to perform CPS assay and PD-L1 expression was unknown.According to the stratified analysis of PD-L1 expression,patients with 5≤CPS<20 and CPS≥20 had≥50%tumor volume reduction with an ORR rate of 100%.While among the patients with CPS<5,1 case got PR≥50%tumor volume reduction and 2 cases of PD with an ORR of 62.5%.The most common adverse reactions were nausea,leukopenia,and anemia.Three patients had abnormal thyroid function,1 had renal impairment,2 had hepatic impairment,and two had pneumonia.There were no grade 3 to 4 adverse reactions.CONCLUSION Locally advanced head and neck squamous carcinoma,especially for patients with advanced stage(IVA/IVB,AICC 8th edition),induction immunotherapy(PD-1 inhibitor)combined with chemotherapy has shown significant short term efficacy,especially for patients with CPS≥5,without serious toxic side effects,and is expected to be a new treatment modality for locally advanced head and neck squamous carcinoma.