PD-1/PD-L1抑制剂联合化疗治疗晚期乳腺癌疗效的Meta分析

摘要/Abstract

摘要： 目的：采用Meta分析方法评价PD-1/PD-L1抑制剂联合化疗与单独化疗对晚期乳腺癌的疗效及安全性，为临床诊断和治疗提供理论依据。方法：检索Pubmed， Embase， Cochrane图书馆从建库至2024年3月以来有关PD-1/PDL1抑制剂联合化疗治疗晚期乳腺癌的文献，由两位研究者独立完成筛选文献、提取资料以及评估偏倚风险后，采用RevMan5.3软件进行统计分析。结果：本次研究共纳入7篇文献。汇总结果表明意向治疗（ITT）人群联合治疗组总生存期（Overall Survival，OS），无进展生存期（Progression-free Survival，PFS）和总缓解率（Overall Remission Rate，ORR）明显优于仅接受化疗的患者(OS：HR=0.90，95%CI 0.82~0.99，P<0.05；PFS：HR=0.80，95%CI 0.74~0.87，P<0.001；ORR：HR=1.17，95%CI 1.07~1.29，P<0.001)。亚组分析进一步表明，免疫治疗对于PD-L1阳性人群的PFS没有显著影响，结果间没有显著差异（HR=0.67，95%CI 0.27~1.63，P=0.37）。免疫治疗在PD-L1阳性人群的OS明显延长（HR=1.36，95% CI 1.01~1.85，P=0.004）。提示联合组不良反应发生率明显高于对照组(RR=1.12，95% CI 1.02~1.22，P=0.02)，联合组≥3级的不良反应发生情况明显高于对照组（RR=1.12，95%CI 1.01~1.85，Z=3.64，P=0.000 3<0.05），联合治疗组甲状腺功能减退症的发生率显著增加（RR，3.78；95%CI，2.85~5.02，P<0.000 01），甲状腺功能亢进（RR，6.95；95%CI，2.51~12.99，P=0.000 2）、咳嗽（RR，1.28；95%CI，1.07~1.53，P=0.006）。结论：PD-1/PD-L1抑制剂联合化疗治疗晚期乳腺癌比单独化疗更有效，但不良反应发生率增加。

关键词: font-size:medium, ">免疫治疗；PD-1/PD-L1；化疗；晚期乳腺癌；Meta分析

Abstract: Objective： Meta analysis method was used to evaluate the efficacy and safety of PD-1/PD-L1 inhibitor combined chemotherapy and chemotherapy alone for advanced breast cancer， providing theoretical basis for clinical diagnosis and treatment. Methods： The Pubmed， Embase， and Cochrane libraries were searched for the literature on PD-1/PDL1 inhibitors combined with chemotherapy for advanced breast cancer from the establishment of the database to March 2024. After the two researchers independently screened the literature， extracted the data， and evaluated the risk of bias， the RevMan5.3 software was used for statistical analysis. Results： A total of 7 articles were included in this study. The summary results showed that the Overall Survival， Progression-free Survival and Overall Remission Rate of the ITT population in the combination therapy group were significantly better than those of patients receiving chemotherapy alone (OS： HR=0.90， 95%CI 0.82-0.99， P<0.05. PFS： HR=0.80， 95%CI 0.74-0.87，P<0.001； ORR：HR=1.17， 95%CI 1.07-1.29， P<0.001). Subgroup analysis further showed that immunotherapy had no significant effect on PFS in the PD-L1 positive population， and there was no significant difference between the results (HR=0.67， 95%CI 0.27-1.63， P=0.37). Immunotherapy significantly prolonged OS in the PD-L1 positive population (HR=1.36， 95% CI 1.01-1.85， P=0.004). This suggests that the incidence of adverse reactions at any level in the combination group was significantly higher than that in the control group (RR=1.12， 95%CI 1.02-1.22， P=0.02)， and the incidence of adverse reactions ≥ grade 3 in the combination group was significantly higher than that in the control group (RR=1.12， 95%CI 1.01-1.85)， Z=3.64，P=0.000 3<0.05）. The incidence of hypothyroidism， hyperthyroidism (RR， 3.78； 95% CI， 2.85-5.02， P<0.000 01)， cough (RR， 1.28； 95% CI， 2.51-12.99， P=0.000 2)， and cough (RR， 1.28； 95% CI， 1.07-1.53， P=0.006) in the combined treatment group were significantly increased (RR， 3.78； 95% CI， 2.85-5.02， P<0.000 01). Conclusion： PD-1/PD-L1 inhibitor combined with chemotherapy is more effective than chemotherapy alone in the treatment of advanced breast cancer， but the combined treatment has a higher incidence of adverse reactions.

Key words: font-size:medium, ">Immunotherapy； PD-1/PD-L1； Chemotherapy； Advanced breast cancer； Meta analysis

中图分类号:

张雪莲1, 王冠杰1, 孙清海1, 王振华1, 谭帅2. PD-1/PD-L1抑制剂联合化疗治疗晚期乳腺癌疗效的Meta分析[J]. 中国药物评价, 2025, 42(1): 61-67.

ZHANG Xuelian1, WANG Guanjie1, SUN Qinghai1, WANG Zhenhua1, TAN Shuai2. Meta Analysis of The Efficacy of Pd-1/Pd-L1 Inhibitor Combined with Chemotherapy In The Treatment of Advanced Breast Cancer[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2025, 42(1): 61-67.

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