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乐伐替尼联合帕博利珠单抗治疗复发性、晚期或转移性子宫内膜癌患者的真实世界结局

Real World Outcomes in Patients With Recurrent, Advanced, or Metastatic Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab.

作者信息

Pawsey A, Mahalingam P, Senthivel N, Ramessur A, Turnbull E, Usman S, Browne R, Patel A, Stewart A, Tookman L, Counsell N, Miller R, Nicum S, Eminowicz G

机构信息

University College London Hospitals NHS Foundation Trust, Oncology, UCLH, 250 Euston Road, NW1 2PG, UK.

Imperial College Healthcare NHS Trust, Oncology, UK.

出版信息

Clin Oncol (R Coll Radiol). 2025 Jan;37:103656. doi: 10.1016/j.clon.2024.10.008. Epub 2024 Oct 11.

Abstract

AIMS

Patients with endometrial cancer who progress following first line therapy have improved survival outcomes with pembrolizumab and lenvatinib (pem/len) compared with standard of care chemotherapy, as demonstrated in KEYNOTE-775. This was in a group of trial patients with good performance status and excluded those with carcinosarcoma histology. In KEYNOTE-775 pem/len was associated with significant toxicity, leading to dose reductions, treatment cessation, and patient morbidity. We set out to assess the tolerability, toxicity and outcomes following pem/len for patients with recurrent, advanced or metastatic endometrial cancer in a real-world setting.

MATERIALS AND METHODS

UK centres treating patients with pem/len for advanced endometrial cancer within the compassionate access programme were approached. Retrospective data were analysed for those treated between May 2022 and June 2023. Data on patient demographics, treatment, toxicity and outcomes were extracted from medical records. Toxicity and tolerability were compared in those over and under the age of 70.

RESULTS

Seven centres returned data for 70 patients. Median age of patients was 68.5 years (range 45-85) with a performance status of 0-1 in 77.1% and of 2 in 22.9%. Histological subtypes included serous (34.3%), endometrioid (32.9%), carcinosarcoma (14.3%), clear cell (7.1%), mixed (2.9%) and other (8.6%). Grade ≥3 toxicity was reported in 55.7% with any-grade toxicity observed in 85.7%. In those aged ≥70 years (n = 30) the rate of grade ≥3 toxicity was 60.0%. Rates of dose reduction of lenvatinib were 64.3%, and toxicity-related treatment interruption was 45.7%. The 6-month progression-free and overall survival rates were 54.0% (95%CI: 39.0-66.8) and 70.1% (95%CI:56.5-80.1) respectively.

CONCLUSION

This real-world, observational study of pem/len showed comparable tolerability, toxicity, and outcomes to previously reported clinical trial data. Our cohort included patients with a poorer PS and a broader range of histological subtypes including carcinosarcoma.

摘要

目的

如KEYNOTE-775试验所示,一线治疗后病情进展的子宫内膜癌患者,与标准护理化疗相比,帕博利珠单抗和乐伐替尼(pem/len)联合使用可改善生存结果。这是在一组身体状况良好的试验患者中进行的,且排除了癌肉瘤组织学类型的患者。在KEYNOTE-775试验中,pem/len与显著的毒性相关,导致剂量减少、治疗中断和患者发病。我们旨在评估在现实环境中,复发、晚期或转移性子宫内膜癌患者使用pem/len后的耐受性、毒性和疗效。

材料与方法

联系了英国在同情用药项目中为晚期子宫内膜癌患者使用pem/len进行治疗的中心。对2022年5月至2023年6月期间接受治疗的患者进行回顾性数据分析。从医疗记录中提取患者人口统计学、治疗、毒性和疗效数据。比较了70岁及以上和70岁以下患者的毒性和耐受性。

结果

七个中心返回了70例患者的数据。患者中位年龄为68.5岁(范围45-85岁),77.1%的患者身体状况评分为0-1,22.9%的患者评分为2。组织学亚型包括浆液性(34.3%)、子宫内膜样(32.9%)、癌肉瘤(14.3%)、透明细胞(7.1%)、混合型(2.9%)和其他(8.6%)。报告≥3级毒性的患者占55.7%,观察到任何级别毒性的患者占85.7%。在年龄≥70岁的患者(n = 30)中,≥3级毒性发生率为60.0%。乐伐替尼的剂量减少率为64.3%,与毒性相关的治疗中断率为45.7%。6个月无进展生存率和总生存率分别为54.0%(95%CI:39.0-66.8)和70.1%(95%CI:56.5-80.1)。

结论

这项关于pem/len的现实世界观察性研究显示,其耐受性、毒性和疗效与先前报告的临床试验数据相当。我们的队列包括身体状况较差的患者以及更广泛的组织学亚型,包括癌肉瘤。

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