Ho Gwo Fuang, Lee Soo Chin, Bustam Anita Zarina, Alip Adlinda, Abdul Satar Nur Fadhlina, Saad Marniza, Malik Rozita Abdul, Lim Siew Eng, Ow Samuel G W, Wong Andrea, Chong Wan-Qin, Ang Yvonne L E, Lee Audrey Weng Yan, Hasan Siti Norhidayu, Tuan Zaid Nabilah, Law Kian Boon, Toh Yok Yong, Tan Hooi Chiao, Selvam Bawani, Lim Joanna, Pan Jia-Wern, Teo Soo Hwang
Clinical Oncology Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Department of Haematology-Oncology, National University Cancer Institute, Singapore.
Lancet Reg Health West Pac. 2025 Jul 13;60:101637. doi: 10.1016/j.lanwpc.2025.101637. eCollection 2025 Jul.
A common germline deletion polymorphism in the gene increases the rate of somatic hypermutation in breast cancer, which in turn is associated with greater neoantigen burden and immune activation. This phase II study evaluated the impact of the deletion polymorphism on the response to pembrolizumab monotherapy in metastatic HER2-negative breast cancer patients.
Eligible patients had a confirmed diagnosis of metastatic HER2-negative breast cancer, 1-3 prior lines of therapy, and documented homozygous or heterozygous germline deletion of . Patients received 200 mg of pembrolizumab intravenously every 3 weeks for up to 2 years. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression-free survival, and overall survival. ClinicalTrials.gov, NCT03989089.
All enrolled patients (N = 44) were women, 30% (12/40) had PD-L1-positive tumours, and 64% (28/44) had received ≥2 previous lines of therapy for metastatic disease. Objective response rate (ORR) was 20% (9/44) (95% CI, 9.8-35.3) in the total and 25% (3/12) (95% CI, 5.5-57.2) in the PD-L1-positive population. Disease control rate (DCR) for the study was 52% (23/44) (95% CI, 36.7-67.5). Median progression-free survival (PFS) was 3.1 months (95% CI, 2.1-4.3), and 6-month PFS rate was 27% (12/44) (95% CI, 16.8-44.2). Median overall survival (OS) was 15.5 months (95% CI, 13.0-26.5), and 12-month OS rate was 66% (29/44) (95% CI, 53.3-82.5). Treatment-related adverse events (AEs) occurred in 30 (68%) patients, including 1 (2%) with a grade 3 AE. There were no deaths due to AEs.
Pembrolizumab monotherapy demonstrated anti-tumour activity in a subset of previously treated metastatic HER2-breast cancer patients with germline deletion.
This study was sponsored by Cancer Research Malaysia, a non-profit cancer research organization. Merck Sharp & Dohme (MSD) provided free access to the trial drug through the Merck Investigator Studies Program.
该基因中一种常见的种系缺失多态性会增加乳腺癌体细胞超突变率，进而与更高的新抗原负荷和免疫激活相关。这项II期研究评估了该缺失多态性对转移性HER2阴性乳腺癌患者接受帕博利珠单抗单药治疗反应的影响。
符合条件的患者确诊为转移性HER2阴性乳腺癌，既往接受过1 - 3线治疗，且有记录显示种系存在纯合或杂合缺失。患者每3周静脉注射200 mg帕博利珠单抗，持续2年。主要终点是客观缓解率。次要终点是疾病控制率、无进展生存期和总生存期。ClinicalTrials.gov，NCT03989089。
所有入组患者（N = 44）均为女性，30%（12/40）的肿瘤为PD - L1阳性，64%（28/44）既往接受过≥2线转移性疾病治疗。总体客观缓解率（ORR）为20%（9/44）（95%CI，9.8 - 35.3），PD - L1阳性人群中为25%（3/12）（95%CI，5.5 - 57.2）。该研究的疾病控制率（DCR）为52%（23/44）（95%CI，36.7 - 67.5）。中位无进展生存期（PFS）为3.1个月（95%CI，2.1 - 4.3），6个月PFS率为27%（12/44）（95%CI，16.8 - 哪里可以找到免费的论文查重软件44.2）。中位总生存期（OS）为15.5个月（95%CI，13.0 - 26.5），12个月OS率为66%（29/44）（95%CI，53.3 - 82.5）。30例（68%）患者发生了与治疗相关的不良事件（AE），包括1例（2%）3级AE。没有因AE导致的死亡。
帕博利珠单抗单药治疗在一部分既往接受过治疗的伴有种系缺失的转移性HER2阴性乳腺癌患者中显示出抗肿瘤活性。
本研究由马来西亚癌症研究组织赞助，这是一个非营利性癌症研究机构。默克雪兰诺（MSD）通过默克研究者研究项目免费提供试验药物。
