PD-1免疫治疗联合贝伐单抗进行抗血管生成双靶治疗Ⅳ期肺腺癌疗效、短期生存及对细胞免疫功能的影响

Efficacy and short-term survival of PD-1 immunotherapy combined with bevacizumab for double-target anti-angiogenic therapy on stageⅣlung adenocarcinoma and its influence on cellular immune function

摘要:

目的： 观察程序性细胞死亡因子1（programmed cell death 1，PD-1）免疫治疗联合贝伐单抗进行抗血管生成双靶治疗Ⅳ期肺腺癌的疗效，并分析其对细胞免疫功能、短期预后和不良反应的影响。方法： 选取成都大学附属医院2018年12月至2020年8月收治的Ⅳ期肺腺癌患者67例，按照治疗方式不同分为对照组（n=33）和联合组（n=34），对照组予以化疗+PD-1抑制剂治疗，联合组予以化疗+PD-1抑制剂+贝伐单抗治疗，比较2组患者近期治疗疗效、治疗前后细胞免疫功能、卡氏功能状态（Karnofsky performance status，KPS）评分变化情况、不良反应及无进展生存期。结果： 联合组患者治疗总有效率和疾病控制率分别为29.41%和79.41%，显著高于对照组的9.09%和54.55%（P<0.05）；治疗后，联合组患者CD3⁺、CD4⁺、CD4⁺/CD8⁺显著高于对照组（P<0.05），CD8⁺与对照组患者比较无统计学差异（P>0.05）；联合组患者KPS评分增加稳定率为73.53%，显著高于对照组患者的45.45%（P<0.05）；联合组患者骨髓抑制、消化道反应、血液毒性、肝肾功能损害及周围神经毒性不良反应发生率与对照组患者比较，差异无统计学意义（P>0.05）；联合组患者中位无进展生存期为9.73个月，对照组患者中位无进展生存期为6.05个月，差异有统计学意义（P<0.05）。结论： PD-1免疫治疗联合贝伐单抗进行抗血管生成双靶治疗Ⅳ期肺腺癌，可明显提高近期治疗疗效，改善患者免疫功能，提高其生存质量，延长其无进展生存时间。

Abstract:

Objective: To observe the efficacy of programmed cell death 1 (PD-1) immunotherapy combined with bevacizumab for double-target anti-angiogenic therapy on stageⅣlung adenocarcinoma, and to analyze its influence on cellular immune function, short-term prognosis and adverse reactions. Methods: A total of 67 patients with stageⅣlung adenocarcinoma admitted to our hospital between December 2018 and August 2020 were selected in this study and they were divided into control group (n=33) and combined group (n=34) according to different treatment methods. Control group were treated with chemotherapy+PD-1 inhibitor, and combined group were treated with chemotherapy+PD-1 inhibitor+bevacizumab. The short-term treatment efficacy, changes of cellular immune function and Karnofsky performance status (KPS) score before and after treatment, adverse reactions and progression-free survival time were compared between the two groups. Results: The total effective rate of treatment and disease control rate of combined group were 29.41%and 79.41%respectively, which were significantly higher than 9.09%and 54.55%of control group (P<0.05). After treatment, the CD3⁺, CD4⁺and CD4⁺/CD8⁺in combined group were significantly higher than those in control group (P<0.05), and there was no significant difference in CD8⁺compared to control group (P>0.05). The increase and stable rate of KPS score of patients in combined group was significantly higher than that in control group (73.53%vs.45.45%) (P<0.05). There were no significant differences in the incidence of adverse reactions such as bone marrow suppression, gastrointestinal reactions, blood toxicity, liver-kidney functional damage and peripheral neurotoxicity in combined group compared with those in control group (P>0.05). The median progression-free survival time were 9.73 months in combined group and were 6.05 months in control group, with significant differences (P<0.05). Conclusion: PD-1 immunotherapy combined with bevacizumab for double-target anti-angiogenic therapy of stageⅣlung adenocarcinoma can significantly enhance the short-term treatment efficacy, improve the immune function, promote the quality of life and prolong the progression-free survival time.