一线PD-1单抗与贝伐单抗双靶联合化疗治疗晚期非鳞非小细胞肺癌临床观察

Clinical observation of PD-1immunotherapy combined with the bevacizumab and the chemotherapy for the advanced non-squamous non-small cell lung cancer

目的观察程序性细胞死亡因子1(PD-1)联合贝伐单抗双靶治疗晚期非鳞非小细胞肺癌(NSCLC)临床疗效和不良反应。方法选取2018-06-03-2023-03-31滨州市人民医院(23例)和滨州市中心医院(24例)收治的经病理学或细胞学确诊为驱动基因阴性(表皮生长因子受体、间变性淋巴瘤酶等野生型)晚期(Ⅳ期)非鳞NSCLC患者作为研究对象,均能耐受联合化疗。采用回顾性资料分析研究方法分为2组,贝伐单抗+化疗组(对照组)24例,具体方案:贝伐珠单抗注射液7.5mg/kg,d1,静脉滴入1h;培美曲塞500mg/m^(2),d1,或吉西他滨850mg/m^(2),d1,d8,或白蛋白紫杉醇260.0mg/m^(2),d1,联合顺铂25mg/m^(2),d1~d3,或卡铂〔血药浓度-时间曲线下面积5g/(L·min)〕,d1,静脉滴入。PD-1抑制剂+贝伐单抗+化疗组(观察组)23例,具体方案:卡瑞利珠单抗或信迪利单抗或替雷利珠单抗200mg,d1,静脉滴入1h,其他药物及剂量同对照组。以上2组均21d为1个治疗周期。比较2组患者无进展生存期(PFS)、临床疗效及不良反应。结果治疗2个周期后,观察组客观缓解率(ORR)为82.61%(19/23),对照组为37.50%(9/24),观察组效果优于对照组,差异有统计学意义,χ^(2)=9.923,P=0.002;观察组疾病控制率(DCR)为95.65%(22/23),对照组为87.50%(21/24),差异无统计学意义,χ^(2)=0.229,P=0.632。治疗期间,观察组Ⅰ~Ⅱ级不良反应发生率在免疫性肺炎(χ^(2)=4.383,P=0.036)和甲状腺功能减退(χ^(2)=4.157,P=0.041)方面高于对照组,差异有统计学意义;2组患者Ⅲ~Ⅳ级免疫性肺炎和甲状腺功能减退差异无统计学意义,均P>0.05;2组患者乏力、消化道反应、血小板下降、贫血、肝功能、高血压各方面不良反应发生率差异无统计学意义,均P>0.05。观察组中位PFS为10.84个月,对照组为8.01个月,差异有统计学意义,χ^(2)=9.985,P=0.002。结论PD-1抑制剂+贝伐单抗双靶联合化疗方案治疗晚期非鳞NSCLC安全有效,双靶联合化疗方案有趋向表明能提高晚期非鳞NSCLC患者治疗的ORR和DCR,一定程度延长PFS,且不增加化疗相关不良反应,患者耐受性良好。

Objective To observe the clinical efficacy and safety of programmed cell death 1(PD-1)immunotherapy combined with bevacizumab for advanced non-squamous non-small cell lung cancer(NSCLC).Methods Totally 47patients with non-squamous NSCLC(stageⅣ),who had the negative driver genes,such as epidermal growth factor receptor,anaplastic lymphoma kinase,and other wild gene type,were selected from June 3,2018to March 31,2023from Binzhou People's Hospital(n=23)and Binzhou Central Hospital(n=24),all of whom were able to accept first-line chemotherapy.The respective study was divided into two groups:the group of chemotherapy+bevacizumab(control group,n=24):Bevacizumab 7.5mg/kg,d1,ivdrip 1h;Pemetrexed 500mg/m^(2),d1or Gemcitabine 850mg/m^(2),d1,d8,or Albumin paclitaxel 260.0mg/m^(2),d1,ivdrip,combined with DDP 25mg/m^(2),d1-d3,or Carboplatin[area under plasma concentration-time curve 5g/(L·min)]ivdrip,d1;the group of PD-1inhibitor+bevacizumab+chemotherapy(observation group,n=23):Carrelizumab or Sindilimab or Tislelizumab 200mg,d1,ivdrip 1h,and the combined specific drugs and dose were the same as the control group.Each of the two groups had a 21-day treatment cycle.The progression-free-survival(PFS),clinical efficacy and adverse reactions were compared between the two groups.Results After two cycles of treatment,the objective remission rate(ORR)of the observation group was 82.61%(19/23),while the control group was 37.50%(9/24),the observation group had better efficacy than the control group,and the difference was statistically significant,χ^(2)=9.923,P=0.002.The disease control rate(DCR)of the observation group was 95.65%(22/23),while the control group was 87.50%(21/24),with no statistically significant difference,χ^(2)=0.229,P=0.632.During the treatment period,the incidence of gradeⅠ-Ⅱadverse reactions in immune pneumonia(χ^(2)=4.383,P=0.036)and hypothyroidism(χ^(2)=4.157,P=0.041)was higher in the observation group than in the control group,and the difference was statistically significant.There was no statistically significant difference between the two groups of patients with gradeⅢ-Ⅳimmune pneumonia and hypothyroidism,both P>0.05.There was no statistically significant difference in the incidence of adverse reactions such as fatigue,gastrointestinal reactions,thrombocytopenia,anemia,liver function,and hypertension between the two groups,with all P>0.05.The median PFS of the observation group was 10.84months,while the control group was 8.01months,with a statistically significant difference,χ^(2)=9.985,P=0.002.Conclusions The doubletarget therapy of PD-1immunotherapy combined with bevacizumab for the advanced non-squamous NSCLC can significantly enhance the efficacy as well as safety of treatment,improve the ORR as well as DCR,prolong the progression-free survival time,but do not increase chemotherapy-related toxicity and adverse reactions.The patients can be well tolerated.