阿替利珠单抗联合白蛋白紫杉醇治疗三阴性乳腺癌的疗效及安全性的Meta 分析
Combined atezolizumab and nab-paclitaxel in the treatment of triple negative breast cancer: a meta-analysis on their efficacy and safety.
机构信息
BMed Science, School of Medicine, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
Adelaide Medical School, The University of Adelaide, North Terrace, Adelaide, 5005, Australia.
出版信息
BMC Cancer. 2022 Nov 5;22(1):1139. doi: 10.1186/s12885-022-10225-y.
BACKGROUND
Triple negative breast cancer (TNBC) is clinically aggressive breast cancer with a poor prognosis. Approximately 20% of TNBC has been found to express programmed death ligand 1 (PD-L1), making it a potential therapeutic target. As a PD-L1 inhibitor, atezolizumab is a recently approved immunotherapeutic drug for TNBC, this meta-analysis (MA) was aimed to review the randomized controlled trial studies (RCTs) of combined atezolizumab and nab-paclitaxel in the treatment of TNBC and synthesize the evidence-based results on its effectiveness and safety.
METHOD
We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).
RESULTS
A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).
CONCLUSION
Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.
TRIAL REGISTRATION
This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).
背景
三阴性乳腺癌（TNBC）是一种侵袭性强、预后差的乳腺癌。约 20%的 TNBC 表达程序性死亡配体 1（PD-L1），使其成为潜在的治疗靶点。阿替利珠单抗是一种 PD-L1 抑制剂，是一种最近批准用于 TNBC 的免疫治疗药物，本荟萃分析（MA）旨在回顾阿替利珠单抗联合 nab-紫杉醇治疗 TNBC 的随机对照试验研究（RCT），并综合其有效性和安全性的循证结果。
方法
我们检索了 PubMed、Embase、EBSCOhost 和 ClinicalTrials.gov 以获取比较阿替利珠单抗联合 nab-紫杉醇与 nab-紫杉醇单药治疗 TNBC 的疗效和安全性的合格 RCT。分析的结局包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和治疗相关不良事件（AEs）。
结果
本 MA 共纳入 6 项 RCT。在疗效方面，阿替利珠单抗联合 nab-紫杉醇虽然未显著延长 OS（HR 0.90，95%CI [0.79, 1.01]，p=0.08），但显著改善了 PFS（HR 0.72，95%CI [0.59, 0.87]，p=0.0006）和 ORR（RR 1.25，95%CI [0.79, 1.01]，p<0.00001）。在安全性方面，阿替利珠单抗联合 nab-紫杉醇组与 nab-紫杉醇单药组之间的任何 AEs、血液学、胃肠道和肝脏 AEs 无统计学显著差异。然而，与阿替利珠单抗联合 nab-紫杉醇相比，nab-紫杉醇单药组的严重 AEs、高等级、皮肤毒性、肺部、内分泌和神经毒性 AEs 显著降低（p 值范围从 <0.00001 到 0.02）。
结论
阿替利珠单抗联合 nab-紫杉醇治疗 TNBC 可改善疗效，但与 nab-紫杉醇单药相比，毒性增加。虽然 nab-紫杉醇单药产生化疗相关 AEs，但阿替利珠单抗联合 nab-紫杉醇产生的 AEs，特别是血液学、肺部、内分泌和神经毒性等免疫相关 AEs。
试验注册
本系统评价的研究工作已在 PROSPERO 上注册（注册号：CRD42022297952）。
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