一项吉西他滨联合卡培他滨与吉西他滨联合卡铂作为一线治疗以及肿瘤浸润淋巴细胞作为晚期三阴性乳腺癌患者预后生物标志物的非劣效性Ⅲ期试验。

A non-inferiority, phase III trial of gemcitabine plus capecitabine gemcitabine plus carboplatin as first-line therapy and tumor-infiltrating lymphocytes as a prognostic biomarker in patients with advanced triple-negative breast cancer.

作者信息

Liu Xiaodong, Zhao Weipeng, Jia Yongsheng, Shi Yehui, Wang Xu, Li Shufen, Zhang Pin, Wang Chen, Hao Chunfang, Tong Zhongsheng

机构信息

Department of Breast Oncology, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

出版信息

Ther Adv Med Oncol. 2024 Dec 3;16:17588359241240304. doi: 10.1177/17588359241240304. eCollection 2024.

DOI:10.1177/17588359241240304

PMID:39634173

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11615979/

Abstract

BACKGROUND

Gemcitabine plus capecitabine (GX) shows survival benefit and manageable safety in patients with advanced triple-negative breast cancer (TNBC) but there is a paucity of phase III trial evidence. We aimed to compare the efficacy and safety of GX with gemcitabine plus carboplatin (GC) as first-line treatment for patients with advanced TNBC and validate the prognostic value of tumor-infiltrating lymphocytes (TILs).

METHODS

Patients with advanced TNBC were randomly assigned 1:1 to receive gemcitabine (1000 mg/m) on days 1 and 8 plus oral capecitabine (1000 mg/m twice a day) on days 1-14, or gemcitabine (1000 mg/m) on days 1 and 8 plus carboplatin area under curve 2 on days 1 and 8. The primary endpoint was progression-free survival (PFS). TILs were analyzed by immunohistochemistry. The margin used to establish non-inferiority was 1.2.

RESULTS

In all, 187 patients were randomly assigned, with 93 in GX and 94 in GC. Median PFS was 6.1 months in the GX arm compared with 6.3 months in the GC arm. The hazard ratio for PFS was 1.148, and a 95% CI was 0.856-1.539, exceeding the non-inferiority margin of 1.2. The median overall survival (OS) was 21.0 months in the GX arm compared with 21.5 months in the GC arm. The safety profile for the GX regimen was superior to the GC regimen, especially regarding hematological toxicity. Patients with high CD8 TILs had significantly longer PFS and OS compared with patients with low CD8 TILs. In the high CD8 TIL group, the GC arm had prolonged PFS and OS compared with the GX arm.

CONCLUSION

The trial did not meet the prespecified criteria for the primary endpoint of PFS in patients with advanced TNBC. Moreover, the GC regimen showed better efficacy compared with the GX regimen in patients with high CD8 TILs. However, the GX regimen should be considered in patients who cannot tolerate hematological toxicity.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT02207335.

摘要

背景

吉西他滨联合卡培他滨（GX）对晚期三阴性乳腺癌（TNBC）患者显示出生存获益且安全性可控，但缺乏III期试验证据。我们旨在比较GX与吉西他滨联合卡铂（GC）作为晚期TNBC患者一线治疗的疗效和安全性，并验证肿瘤浸润淋巴细胞（TILs）的预后价值。

方法

晚期TNBC患者按1:1随机分组，分别在第1天和第8天接受吉西他滨（1000mg/m²），并在第1 - 14天接受口服卡培他滨（1000mg/m²，每日两次），或在第1天和第8天接受吉西他滨（1000mg/m²）加第1天和第8天的曲线下面积为2的卡铂。主要终点是无进展生存期（PFS）。通过免疫组织化学分析TILs。用于确定非劣效性的界值为1.2。

结果

总共187例患者被随机分组，其中93例接受GX治疗，94例接受GC治疗。GX组的中位PFS为6.1个月，而GC组为6.3个月。PFS的风险比为1.148，95%置信区间为0.856 - 1.539，超过了1.2的非劣效性界值。GX组的中位总生存期（OS）为21.0个月，而GC组为21.5个月。GX方案的安全性优于GC方案，尤其是在血液学毒性方面。CD8 TILs高的患者与CD8 TILs低的患者相比，PFS和OS显著更长。在高CD8 TIL组中，GC组与GX组相比，PFS和OS有所延长。