全国精准肿瘤学试点研究：韩国精准医学网络集团基于基因组改变的分子谱分析指导的晚期实体瘤治疗的研究（KOSMOS）KCSG AL-20-05。

Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05.

机构信息

Department of Internal Medicine, Division of Hematology and Medical Oncology, Seoul National University Hospital, Seoul.

Department of Oncology, University of Ulsan College of Medicine, Aan Medical Center, Seoul.

出版信息

ESMO Open. 2024 Oct;9(10):103709. doi: 10.1016/j.esmoop.2024.103709. Epub 2024 Sep 20.

DOI:10.1016/j.esmoop.2024.103709

PMID:39305545

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11440300/

Abstract

BACKGROUND

Next-generation sequencing (NGS) has become widely available but molecular profiling-guided therapy (MGT) had not been well established in the real world due to lack of available therapies and expertise to match treatment. Our study was designed to test the feasibility of a nationwide platform of NGS-guided MGT recommended by a central molecular tumor board (cMTB) for metastatic solid tumors.

PATIENTS AND METHODS

Patients with advanced or metastatic solid tumors with available NGS results and without standard treatment were enrolled. The cMTB interpreted the patients' NGS reports and recommended the following: (i) investigational medicinal products (IMPs) approved in other indications; (ii) alternative treatments; (iii) clinical trials. The primary variables were the proportion of patients with actionable genomic alterations and those receiving MGT as per cMTB recommendations. Others included treatment duration (TD), overall response rate (ORR), disease control rate (DCR), and safety.

RESULTS

From February 2021 to February 2022, 193 cases [99 (51.3%) men; median age 58 years (range 24-88 years); median line of previous treatment 3 (range 0-9)] from 29 sites were enrolled for 60 cMTB sessions. The median time from case submission to cMTB discussion was 7 days (range 2-20 days), and to IMP treatment initiation was 28 days (range 14-90 days). Actionable genetic alterations were found in 145 patients (75.1%). A total of 89 (46.1%) patients received actual dosing of IMPs, and 10 (5.2%) were enrolled in cMTB-recommended clinical trials, achieving an MGT rate of 51.3%. ORR and DCR of IMPs were 10.1% and 72.5%, respectively. The median TD was 3.5 months [95% confidence interval (CI) 2.8-5.5 months], and the 4-month TD rate was 44.9%. The median overall survival of patients who received IMPs was 6.9 months (95% CI 5.2-10.0 months).

CONCLUSION

KOSMOS confirmed the feasibility of MGT recommended by the cMTB, achieving a high MGT match rate and promising effectiveness in heavily pretreated advanced cancer patients.

摘要

背景

下一代测序（NGS）已广泛应用，但由于缺乏可用的治疗方法和与之匹配的专业知识，分子谱分析指导的治疗（MGT）尚未在实际中得到很好的建立。我们的研究旨在测试由中央分子肿瘤委员会（cMTB）推荐的全国性 NGS 指导 MGT 平台对转移性实体瘤的可行性。

患者和方法

纳入有可用 NGS 结果且无标准治疗的晚期或转移性实体瘤患者。cMTB 解读患者的 NGS 报告并推荐以下内容：（i）其他适应证批准的研究性药物（IMP）；（ii）替代治疗；（iii）临床试验。主要变量是具有可操作基因组改变的患者比例和根据 cMTB 建议接受 MGT 的患者比例。其他变量包括治疗持续时间（TD）、总缓解率（ORR）、疾病控制率（DCR）和安全性。

结果

从 2021 年 2 月至 2022 年 2 月，来自 29 个地点的 193 例[99 例（51.3%）为男性；中位年龄 58 岁（范围 24-88 岁）；中位既往治疗线数为 3 条（范围 0-9 条）]参加了 60 次 cMTB 会议。病例提交至 cMTB 讨论的中位时间为 7 天（范围 2-20 天），至 IMP 治疗开始的中位时间为 28 天（范围 14-90 天）。在 145 例患者（75.1%）中发现了可操作的遗传改变。共有 89 例（46.1%）患者接受了 IMP 的实际剂量治疗，10 例（5.2%）患者入组了 cMTB 推荐的临床试验，实现了 MGT 率为 51.3%。IMP 的 ORR 和 DCR 分别为 10.1%和 72.5%。IMP 的 TD 中位数为 3.5 个月[95%置信区间（CI）为 2.8-5.5 个月]，4 个月 TD 率为 44.9%。接受 IMP 治疗的患者的中位总生存期为 6.9 个月（95%CI 为 5.2-10.0 个月）。