pembrolizumab治疗复发性lynch样子宫内膜癌与散发性微卫星不稳定性子宫内膜癌（NCT02899793）的2期试验：最新的生存和反应分析

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-05-06 DOI:10.1016/j.ygyno.2025.04.591

Victoria M. Ettorre , Stefania Bellone , Michelle Greenman , Blair McNamara , Luca Palmieri , Namrata Sethi , Cem Demirkiran , Katyayani Papatla , Aparna Kailasam , Eric R. Siegel , Elena Ratner , Alessandro D. Santin

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引用次数: 0

摘要

目的微卫星不稳定性高(MSI-H)/错配修复缺陷（dMMR）是免疫检查点抑制剂应答的生物标志物。我们报告了最新的结果，包括复发铂耐药、MSI-H、子宫内膜癌（EC）患者的5年随访的客观缓解率、无进展生存期和总生存期数据，这些患者使用全外显子组测序（WES）完全测序，并在一项前瞻性II期研究中使用派姆单抗（NCT02899793）进行治疗。方法采用全外显子组测序和FoundationOne平台对经免疫组织化学、聚合酶链反应和MLH-1甲基化检测证实的MSI-H/dMMR子宫内膜癌患者进行测序，鉴定Lynch、Lynch样和MLH-1甲基化特征，然后每3周接受200 mg派姆单抗治疗，持续24个月。主要终点是客观缓解率（ORR），次要终点是无进展生存期（PFS）和总生存期（OS）。结果在几乎97人年的随访后，MSI-H/dMMR患者的Lynch-like亚组（n = 6）继续表现出比甲基化（n = 18）亚组更好的ORR(100%对44%，Fisher’s精确P = 0.024)，以及改善的PFS（未达到Lynch-like对14.6个月，Log-Rank P = 0.005）和改善的OS（未达到Lynch-like对32.6个月，Log-Rank P = 0.058）。两组MSI-H患者的毒性均可控。成熟的随访结果继续表明，lynch样与甲基化MSI-H/dMMR特征在派姆单抗治疗的子宫内膜癌患者的ORR、PFS和OS方面具有预后意义。在未来的MSI-H/dMMR子宫内膜癌患者的免疫检查点抑制剂临床试验中，可能需要对这些转化方面进行分层。

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A phase 2 trial of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability (NCT02899793): Updated survival and response analyses

Objective

Microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) is a biomarker for response to immune checkpoint inhibitors. We report updated results including objective response rate, progression free survival, and overall survival data with 5-year follow-up in recurrent platinum-resistant, MSI-H, endometrial cancer (EC) patients fully sequenced using whole exome sequencing (WES) and treated within a prospective phase II study with pembrolizumab (NCT02899793).

Methods

Tumors from patients with measurable MSI-H/dMMR endometrial cancer confirmed by immunohistochemistry, polymerase chain reaction, and MLH-1 methylation assays were sequenced using whole exome sequencing and the FoundationOne platform for the identification of Lynch, Lynch-like, and MLH-1 methylated characteristics before receiving pembrolizumab 200 mg every 3 weeks for up to 24 months. The primary endpoint was objective response rate (ORR), and secondary endpoints were progression free survival (PFS), and overall survival (OS).

Results

After almost 97 person-years of follow-up, the Lynch-like subgroup (n = 6) of MSI-H/dMMR patients continues to exhibit better ORR than the methylated (n = 18) subgroup (100 % versus 44 %, Fisher's exact P = 0.024), as well as improved PFS (unreached for Lynch-like versus 14.6 months, Log-Rank P = 0.005) and improved OS (unreached for Lynch-like versus 32.6 months, Log-Rank P = 0.058). Toxicity was manageable in both groups of MSI-H patients.

Conclusion

Mature follow-up results continue to suggest the prognostic significance of Lynch-like versus methylated MSI-H/dMMR features in endometrial cancer patients treated with pembrolizumab in terms of ORR, PFS, and OS. Stratification for these translational aspects may be warranted in future clinical trials with immune checkpoint inhibitors in MSI-H/dMMR endometrial cancer patients.

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy