仑伐替尼联合帕博利珠单抗治疗晚期和复发性子宫内膜癌患者的疗效和安全性：系统评价和荟萃分析。
Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis.
机构信息
Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhengzhou Key Laboratory of Early Diagnosis for Gynecological Diseases, Zhengzhou, China.
出版信息
Front Immunol. 2024 Aug 9;15:1404669. doi: 10.3389/fimmu.2024.1404669. eCollection 2024.
BACKGROUND
Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer.
METHODS
We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR).
RESULTS
Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively.
CONCLUSION
Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.
背景
多项试验表明，仑伐替尼联合帕博利珠单抗可使晚期或复发性子宫内膜癌患者获益，无论错配修复（MMR）状态或组织学亚型如何。此前的大多数试验样本量较小。在此，我们旨在评估仑伐替尼联合帕博利珠单抗在晚期和复发性子宫内膜癌患者中的报告疗效和安全性。
方法
我们利用 Cochrane 图书馆、PubMed、Web of Science 和 Embase 数据库，确定了评估仑伐替尼联合帕博利珠单抗在晚期和复发性子宫内膜癌患者中的疗效和安全性的临床试验。分析的结果是无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）和不良事件（AE）的发生率。根据 MMR 状态（缺陷型、dMMR 或功能型、pMMR）进行亚组分析。
结果
纳入四项试验（582 例患者）。汇总的 ORR 为 32.7%（95%CI：28.9-36.5）。亚组分析显示，dMMR 组的 ORR 为 48.1%（95%CI：26.1-70.2），pMMR 组的 ORR 为 33.1%（95%CI：25.7-40.6）。汇总的 DCR 为 74.9%（95%CI：71.3-78.4%）。亚组分析显示，dMMR 组的 DCR 为 81.0%（95%CI：64.5-97.6），pMMR 组的 DCR 为 76.3%（95%CI：66.3-86.3）。所有纳入的研究均报告了随访情况。PFS 和 OS 的中位时间范围分别为 5.3 个月-258 天和 17.2 个月-未达到。关于安全性，任何级别 AE 和≥3 级 AE 的总体汇总比例分别为 95.8%（95%CI：89.5-100.0）和 80.2%（95%CI：59.9-100.0）。
结论
仑伐替尼联合帕博利珠单抗在晚期和复发性子宫内膜癌患者中具有显著的临床获益和毒性。需要进一步的研究来涵盖长期结果。
系统综述注册
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/，标识符 CRD42024522160。
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