| 江婷,罗伊扬,叶子翔,施成炜,王彬彬.PD-1/PD-L1抑制剂联合化疗对比化疗一线治疗晚期非小细胞肺癌疗效及安全性的Meta分析:基于12项多中心、III期、随机对照试验[J].浙江中西医结合杂志,2023,33(5): |
| PD-1/PD-L1抑制剂联合化疗对比化疗一线治疗晚期非小细胞肺癌疗效及安全性的Meta分析:基于12项多中心、III期、随机对照试验 |
| The efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy compared with chemotherapy alone as the first-line treatment for advanced non-small cell lung cancer: A Meta-analysis based on 12 multi-center, phase III, randomized controlled trials |
| 投稿时间：2022-01-26 修订日期：2023-03-27 |
| DOI： |
| 中文关键词: PD-1/PD-L1抑制剂 化疗 非小细胞肺癌 疗效及安全性 Meta分析 |
| 英文关键词:PD-1/PD-L1 inhibitors Chemotherapy Non-small cell lung cancer The efficacy and safety Meta-analysis |
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| 摘要点击次数: 605 |
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| 中文摘要: |
| 目的 旨在系统评价化疗联合程序性死亡受体-1（programmed death-1，PD-1）/程序性死亡-配体1（programmed death-ligand 1，PD-L1）抑制剂对比化疗一线治疗晚期非小细胞肺癌（non-small lung cancer, NSCLC）的疗效及安全性。方法 检索PubMed、Cochrane Library、Embase、Web of science中收录的PD-1/PD-L1抑制剂联合化疗对比化疗一线治疗晚期NSCLC的III期前瞻性、随机对照试验（randomized controlled trials，RCTs），采用Review manager 5.3软件进行Meta分析。结果 纳入12项III期RCTs共6090例晚期NSCLC，其中试验组3464例，对照组2626例。Meta分析结果显示，与单独化疗相比，PD-1/PD-L1抑制剂联合化疗可显著延长OS（HR=0.74，95%CI:[0.67, 0.82]，P<0.00001）和PFS（HR=0.57，95%CI:[0.53, 0.62]，P<0.00001），同时提高了ORR（RR=1.59，95%CI:[1.42, 1.77]，P<0.00001）和DCR（RR=1.76，95%CI:[1.33, 2.33]，P<0.0001），差异均具有统计学意义。同时，与化疗组相比，联合治疗组1-5级和3-5级治疗相关不良反应（treatment-related aside effects，TRAE）的发生率略有增加（RR=1.04，95%CI:[1.02, 1.06]，P<0.0001）、（RR=1.19，95%CI:[1.07, 1.33]，P=0.002），差异具有统计学意义。亚组分析显示，不论是鳞癌或非鳞癌，联合治疗组的OS（HR=0.73，95%CI:[0.66, 0.81]，P<0.00001）和PFS（HR=0.57，95%CI:[0.53, 0.62]，P<0.00001）均显著优于化疗组。联合治疗在PD-L1≥50%和PD-L1<1人群能观察OS的获益（HR=0.65，95%CI:[0.47, 0.91]）、（HR=0.80，95%CI:[0.69, 0.92]），但在PD-L1 1%-49%人群中OS获益不明显（HR=1.01，95%CI:[0.82, 1.24]）。不论PD-L1表达高低，均能观察到PFS获益（HR=0.57，95%CI:[0.52, 0.64]，P<0.00001），差异具有统计学意义。结论 PD-1/PD-L1抑制剂联合化疗较单独化疗一线治疗晚期NSCLC可显著延长患者的OS、PFS，提高ORR、DCR，但总体不良反应较化疗略高。同时，联合治疗模式的生存获益在PD-L1≥50%和PD-L1<1%人群中更具优势，但不受病理类型的影响。 |
| 英文摘要: |
| Objective To systematically evaluate the efficacy and safety of chemotherapy combined with programmed death-1（PD-1）/programmed death-ligand 1（PD-L1） inhibitors compared with chemotherapy alone as the first-line treatment of advanced non-small lung cancer (NSCLC). Methods Search in the PubMed, Cochrane Library, Embase, Web of science databases for phase III prospective, randomized controlled trials (RCTs) related to PD-1/PD-L1 inhibitors combined with chemotherapy compared to chemotherapy as the first-line treatment of advanced NSCLC. We use Review manager 5.3 software to complete Meta analysis. Results A total of 12 eligible phase III RCTs with 6090 advanced NSCLC patients were enrolled including 3464 cases in the experimental group and 2626 cases in the control group. Meta-analysis results showed that compared with chemotherapy alone, PD-1/PD-L1 inhibitor combined with chemotherapy can significantly prolong OS (HR=0.74, 95%CI: [0.67, 0.82], P<0.00001) and PFS（HR=0.57，95%CI:[0.53, 0.62]，P<0.00001）, with the increasing rates in ORR (RR=1.59, 95%CI: [1.42, 1.77], P<0.00001) and DCR (RR=1.76, 95%CI) :[1.33, 2.33], P<0.0001), the difference was statistically significant. Meanwhile, compared with the chemotherapy group, the incidence of grade 1-5 and grade 3-5 treatment-related aside effects（TRAE） in the combined treatment group increased slightly (RR=1.04, 95%CI: [1.02, 1.06], P<0.0001), (RR= 1.19, 95%CI: [1.07, 1.33], P=0.002), the difference was statistically significant. Subgroup analysis showed the improved benefits of OS in people with PD-L1≥50% and PD-L1<1 was observe in the combinative therapy than chemotherapy alone (HR=0.65, 95%CI: [0.47, 0.91])、(HR=0.80, 95%CI: [0.69, 0.92]), but in the PD-L1 1%-49% population, OS benefit is not obvious (HR=1.01, 95%CI: [0.82, 1.24]). Regardless of the level of PD-L1 expression, PFS benefits can be observed (HR=0.57, 95%CI: [0.52, 0.64], P<0.00001), and the difference is statistically significant. whether it was squamous cell carcinoma or non-squamous cell carcinoma, the OS (HR=0.73, 95%CI: [0.66, 0.81], P<0.00001) and PFS benefits (HR=0.59, 95%CI: [ 0.55, 0.62], P<0.00001) were significantly better than the chemotherapy group. Conclusion The combinative therapy of PD-1/PD-L1 inhibitors with chemotherapy can significantly improve the OS, PFS, ORR and DCR of patients with advanced NSCLC compared with chemotherapy alone as the first-line treatment, but the overall side effects are slightly higher than chemotherapy. in addition, the survival benefit of the combinative treatment is more advantageous in population with PD-L1≥50% and PD-L1<1%, but is not affected by the pathological type. |
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