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韩国 2010-2020 年应用分子检测和靶向治疗的非小细胞肺癌生存率趋势

Trends in Survival Rates of Non-Small Cell Lung Cancer With Use of Molecular Testing and Targeted Therapy in Korea, 2010-2020.

机构信息

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.

Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

出版信息

JAMA Netw Open. 2023 Mar 1;6(3):e232002. doi: 10.1001/jamanetworkopen.2023.2002.

Abstract

IMPORTANCE

Over the past 10 years, treatment of non-small cell lung cancer (NSCLC) has been continually revolutionized. However, standard clinical trials may not reflect current multiple lines of treatment and corresponding outcomes in a timely manner.

OBJECTIVE

To investigate outcomes associated with new treatment of NSCLC in a clinical setting.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with NSCLC between January 1, 2010, and November 30, 2020, who received any anticancer treatment at Samsung Medical Center in Korea. Data were analyzed from November 2021 through February 2022.

EXPOSURES

Clinical and pathological stage, histology, and major druggable sequence variation, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1, RET, MET exon 14 skipping, BRAF V600E, KRAS G12C, and NTRK between 2 periods (period I: 2010-2015 vs period II: 2016-2020).

MAIN OUTCOMES AND MEASURES

The primary outcome was the 3-year survival rate of NSCLC. Secondary outcomes included median overall survival, progression-free survival, and recurrence-free survival.

RESULTS

Among 21 978 patients with NSCLC (median [range] age at diagnosis, 64.1 [57.0-71.0] years; 13 624 males [62.0%]), there were 10 110 patients in period I and 11 868 patients in period II; adenocarcinoma (AD) was the predominant histology (7112 patients [70.3%] in period I and 8813 patients [74.3%] in period II). There were 4224 never smokers [41.8%] in period I and 5292 never smokers [44.6%] in period II. Compared with patients in period I, patients during period II were more likely to undergo molecular tests in the AD (5678 patients [79.8%] vs 8631 patients [97.9%]) and non-AD (1612 of 2998 patients [53.8%] and 2719 of 3055 patients [89.0%]) groups. In patients with AD in period I, 3-year survival rates were 92.8% (95% CI, 91.8%-93.7%), 72.4% (95% CI, 68.3%-76.8%), 56.7% (95% CI, 53.4%-60.2%), and 28.7% (95% CI, 27.0%-30.4%) for stage I, II, III, and IV, respectively. In period II, 3-year survival rates of patients with AD were 95.1% (95% CI, 94.4%-95.9%), 82.5% (95% CI, 79.1%-86.1%), 65.1% (95% CI, 61.8%-68.6%), and 42.4% (95% CI, 40.3%-44.7%) for each stage, respectively. In patients without AD, 3-year survival rates were 72.0% (95% CI, 68.8%-75.3%), 60.0% (95% CI, 56.2%-64.1%), 38.9% (95% CI, 35.6%-42.5%), and 9.7% (95% CI, 7.9%-12.1%) for each stage in period I. In period II, the 3-year survival rates of patients without AD were 79.3% (95% CI, 76.3%-82.4%), 67.3% (95% CI, 62.8%-72.1%), 48.2% (95% CI, 44.5%-52.3%), and 18.1% (95% CI, 15.1%-21.6%) for each stage.

CONCLUSIONS AND RELEVANCE

In this cohort study of 10 years of clinical data, survival outcomes were improved across all stages, with larger increases in patients with stage III to IV disease. The incidence of never-smokers and the use of molecular testing increased.

摘要

重要性

在过去的 10 年中,非小细胞肺癌(NSCLC)的治疗不断发生变革。然而,标准临床试验可能无法及时反映当前的多种治疗方法和相应的结果。

目的

调查临床环境中 NSCLC 新治疗方法的相关结果。

设计、设置和参与者:这项队列研究纳入了 2010 年 1 月 1 日至 2020 年 11 月 30 日期间在韩国三星医疗中心接受任何抗癌治疗的 NSCLC 患者。数据于 2021 年 11 月至 2022 年 2 月进行分析。

暴露情况

临床和病理分期、组织学以及主要的可靶向序列变异,包括表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)、ROS1、RET、外显子 14 跳跃、BRAF V600E、KRAS G12C 和 NTRK,两个时期(时期 I:2010-2015 年 vs 时期 II:2016-2020 年)之间的差异。

主要结局和测量指标

主要结局是 NSCLC 的 3 年生存率。次要结局包括中位总生存期、无进展生存期和无复发生存期。

结果

在 21978 例 NSCLC 患者中(诊断时的中位年龄[范围],64.1[57.0-71.0]岁;男性 13624 例[62.0%]),10110 例患者在时期 I,11868 例患者在时期 II;腺癌(AD)是主要的组织学类型(时期 I 中有 7112 例[70.3%],时期 II 中有 8813 例[74.3%])。4224 例从不吸烟者[41.8%]在时期 I,5292 例从不吸烟者[44.6%]在时期 II。与时期 I 相比,时期 II 中 AD(5678 例[79.8%] vs 8631 例[97.9%])和非 AD(1612 例[53.8%]和 2719 例[89.0%])患者接受分子检测的可能性更高。在时期 I 中 AD 患者中,各分期的 3 年生存率分别为 92.8%(95%CI,91.8%-93.7%)、72.4%(95%CI,68.3%-76.8%)、56.7%(95%CI,53.4%-60.2%)和 28.7%(95%CI,27.0%-30.4%)。在时期 II 中,AD 患者的 3 年生存率分别为 95.1%(95%CI,94.4%-95.9%)、82.5%(95%CI,79.1%-86.1%)、65.1%(95%CI,61.8%-68.6%)和 42.4%(95%CI,40.3%-44.7%)。在非 AD 患者中,各分期的 3 年生存率分别为 72.0%(95%CI,68.8%-75.3%)、60.0%(95%CI,56.2%-64.1%)、38.9%(95%CI,35.6%-42.5%)和 9.7%(95%CI,7.9%-12.1%)。在时期 II 中,非 AD 患者的 3 年生存率分别为 79.3%(95%CI,76.3%-82.4%)、67.3%(95%CI,62.8%-72.1%)、48.2%(95%CI,44.5%-52.3%)和 18.1%(95%CI,15.1%-21.6%)。

结论和相关性

在这项为期 10 年的临床数据队列研究中,所有分期的生存结果均得到改善,III 期至 IV 期疾病患者的改善幅度更大。从不吸烟者的发病率和分子检测的使用有所增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/337d/10020884/70c2cb68c86f/jamanetwopen-e232002-g001.jpg

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