基于全国性数据库的回顾性研究：通过综合基因组分析鉴定的伴有（PD-L1基因）扩增的实体瘤的免疫检查点抑制剂疗效评估

Evaluation of immune checkpoint inhibitor efficacy for solid tumors with (PD-L1 gene) amplification identified by comprehensive genomic profiling: retrospective study based on a nationwide database.

作者信息

Nakayama Tomohiro, Takahama Takayuki, Chiba Yasutaka, Shiraishi Naoki, Kawakami Hisato, Yonesaka Kimio, Nakagawa Kazuhiko, Hayashi Hidetoshi

机构信息

Medical Oncology, Kishiwada City Hospital, Kishiwada, Japan.

Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.

出版信息

J Immunother Cancer. 2024 Dec 18;12(12):e010130. doi: 10.1136/jitc-2024-010130.

DOI:10.1136/jitc-2024-010130

PMID:39694703

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11667388/

Abstract

BACKGROUND

Amplification of the programmed cell death-ligand 1 gene () is highly prevalent and associated with a high response rate to immune checkpoint inhibitors (ICIs) in lymphomas, and is also a potential biomarker for ICI treatment of solid tumors. However, the efficacy of ICIs for solid tumors with amplification identified by comprehensive genomic profiling (CGP) has been unclear. We here examined ICI efficacy for solid tumors with amplification identified by CGP in a national database.

METHODS

We retrospectively analyzed data from the Center for Cancer Genomics and Advanced Therapeutics database containing 60,155 CGP test results for individuals with solid tumors. Only clinical data from patients treated with ICIs alone (not those undergoing concomitant therapy with molecularly targeted or cytotoxic chemotherapeutic agents) were evaluated. We matched 48 patients in the amplification-positive group with 170 patients in the amplification-negative group in a 1:4 ratio based on tumor type, histology, treatment, and age. Overall survival (OS), time to next treatment (TTNT), and response rate were evaluated as treatment outcomes in the two groups.

RESULTS

OS was similar in the -amplified and matched -non-amplified groups (median of 22.1 vs 26.3 months, respectively; HR of 0.92 with a 95% CI of 0.55 to 1.54; p=0.075). TTNT tended to be longer in the -amplified group than in the matched -non-amplified group (median of 16.5 vs 14.0 months; HR of 0.63 with a 95% CI of 0.37 to 1.08; p=0.091). The objective response rate was 33.3% and 18.4% (difference of 14.9%, with a 95% CI of -0.2% to 31.6%), and the disease control rate was 63.9% and 41.1% (difference of 22.8%, with a 95% CI of 5.1% to 40.4%), in the -amplified and matched -non-amplified groups, respectively.

CONCLUSIONS

The number of patients with solid tumors positive for amplification in this analysis is the largest to date, and our results suggest that such gene amplification may be associated with the outcome of ICI treatment in such individuals. amplification identified by CGP may therefore be a predictor of ICI efficacy for solid tumors.

TRIAL REGISTRATION NUMBER

UMIN000029779.

摘要

背景

程序性细胞死亡配体1基因（）扩增在淋巴瘤中高度普遍，且与对免疫检查点抑制剂（ICI）的高反应率相关，也是ICI治疗实体瘤的潜在生物标志物。然而，通过综合基因组分析（CGP）鉴定出的具有扩增的实体瘤接受ICI治疗的疗效尚不清楚。我们在此研究了在一个国家数据库中，通过CGP鉴定出具有扩增的实体瘤接受ICI治疗的疗效。

方法

我们回顾性分析了癌症基因组学与先进治疗中心数据库中的数据，该数据库包含60155例实体瘤患者的CGP检测结果。仅评估了单独接受ICI治疗的患者（未接受分子靶向或细胞毒性化疗药物联合治疗的患者）的临床数据。我们根据肿瘤类型、组织学、治疗和年龄，以1:4的比例将扩增阳性组的48例患者与扩增阴性组的170例患者进行匹配。评估两组的总生存期（OS）、下次治疗时间（TTNT）和缓解率作为治疗结果。

结果

扩增组和匹配的非扩增组的OS相似（中位数分别为22.1个月和26.3个月；风险比为0.92，95%置信区间为0.55至1.54；p = 0.075）。扩增组的TTNT倾向于比匹配的非扩增组长（中位数分别为16.5个月和14.0个月；风险比为0.63，95%置信区间为0.37至1.08；p = 0.091）。扩增组和匹配的非扩增组的客观缓解率分别为33.3%和18.4%（差异为14.9%，95%置信区间为-0.2%至31.6%），疾病控制率分别为63.9%和41.1%（差异为22.8%，95%置信区间为5.1%至40.4%）。