接受多西他赛治疗的 KRAS 突变晚期非小细胞肺癌临床试验参与者的脑转移情况：汇总数据分析

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-07-01 DOI:10.1016/j.lungcan.2024.107854

Jacob Aptekar , Rahul Jain , Beata Korytowsky , Afrah Shafquat , Jacob Hendershot , Aniketh Talwai , Yahav Itzkovich , Sukhmani K. Padda

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引用次数: 0

摘要

目的目前有关KRAS突变（KRASmut）晚期非小细胞肺癌（NSCLC）标准疗法对中枢神经系统（CNS）疗效的数据有限。本研究的目的是利用历史临床试验的汇总数据，调查接受多西他赛治疗的 KRAS 突变晚期 NSCLC 脑转移的发生率和进展情况。分析对象仅限于ⅢB-Ⅳ期KRAS突变NSCLC，且在接受≥1次全身抗癌治疗后疾病出现进展。无症状、接受过治疗和脑转移病情稳定的参与者均被纳入研究范围。终点包括12个月的中枢神经系统疾病控制率（CNS-DCR）和根据《实体瘤反应评估标准》得出的中枢神经系统进展情况、无进展生存期（PFS）和总生存期（OS）。结果共有595名参与者参与了分析（62人[10%]有基线脑转移，533人[90%]无脑转移）。在有脑转移的参与者中，有17人（27.4%）在多西他赛治疗期间出现中枢神经系统进展，12个月的中枢神经系统-DCR为75.8%；45人（8.4%）没有基线脑转移，但在治疗期间出现了脑转移。在一项仅限于转移性疾病患者的分析中，有基线脑转移和无基线脑转移的结果分别为：中位 PFS，3.3 个月和 4.9 个月（p <0.005）；12 个月 PFS，5% 和 16%；中位 OS，6.9 个月和 10.4 个月（p <0.005）；12 个月 OS，20% 和 44%。结论这些研究结果确定了多西他赛在既往接受过治疗的KRAS突变晚期NSCLC患者中的中枢神经系统进展率，有助于解释正在进行的新型KRAS靶向治疗策略与多西他赛的随机临床试验数据。

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Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis

Objectives

Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials.

Materials and Methods

Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status.

Results

A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively.

Conclusion

These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.