Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.

IF 41.6 1区 医学 Q1 ONCOLOGY Lancet Oncology Pub Date : 2024-08-01 Epub Date: 2024-07-25 DOI:10.1016/S1470-2045(24)00313-9
Xin Liu, Xiaowei Zhang, Shiyu Jiang, Miao Mo, Qifeng Wang, Yanli Wang, Liangping Zhou, Silong Hu, Huijuan Yang, Yifeng Hou, Yong Chen, Xueguan Lu, Yu Wang, Xiaoyan Zhou, Wentao Li, Cai Chang, Xiujiang Yang, Ke Chen, Jun Cao, Qinghua Xu, Yifeng Sun, Jianfeng Luo, Zhiguo Luo, Xichun Hu
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We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP.</p><p><strong>Methods: </strong>This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m<sup>2</sup> by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m<sup>2</sup> or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m<sup>2</sup> by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600).</p><p><strong>Findings: </strong>Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed.</p><p><strong>Interpretation: </strong>This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients.</p><p><strong>Funding: </strong>Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT.</p><p><strong>Translation: </strong>For the Chinese translation of the abstract see Supplementary Materials section.</p>","PeriodicalId":17942,"journal":{"name":"Lancet Oncology","volume":null,"pages":null},"PeriodicalIF":41.6000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/S1470-2045(24)00313-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP.

Methods: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600).

Findings: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed.

Interpretation: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients.

Funding: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.

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90基因表达检测指导下的部位特异性治疗与原发灶不明癌症患者的经验性化疗(复旦CUP-001):随机对照试验。
背景:经验性化疗仍是原发灶不明的恶性肿瘤(CUP)患者的标准治疗方法。目前已开发出基因表达谱分析方法来确定 CUP 患者的原发组织,但其临床疗效尚未得到证实。我们的目的是评估 90 个基因表达检测法与经验性化疗相比,对 CUP 患者进行部位特异性治疗的有效性和安全性:这项随机对照试验在复旦大学上海肿瘤中心(中国上海)进行。我们招募了年龄在18-75岁之间、既往未接受过治疗的CUP患者(组织学证实为转移性腺癌、鳞癌、分化不良癌或分化差的肿瘤),以及东部合作肿瘤学组(ECOG)表现状态为0-2、无法接受局部根治性治疗的患者。患者按波科克和西蒙最小化法随机分配(1:1)接受部位特异性治疗或经验性化疗(紫杉类药物[第1天静脉注射175毫克/平方米]加铂类药物[第1天静脉注射顺铂75毫克/平方米或卡铂曲线下面积5],或吉西他滨[第1天和第8天静脉注射1000毫克/平方米]加铂类药物[同上])。最小化因素为 ECOG 表现状态和疾病程度。临床医生和患者均未被蒙蔽。特定部位治疗组的肿瘤来源可通过 90 基因表达检测进行预测,并据此进行治疗。主要终点是意向治疗人群的无进展生存期。试验已经结束,分析结果也已完成。该研究已在ClinicalTrials.gov(NCT03278600)上注册:2017年9月18日至2021年3月18日期间,182名患者(男性105人[58%],女性77人[42%])被随机分配接受部位特异性治疗(91人)或经验性化疗(91人)。在部位特异性治疗组中,最常预测的五个原发组织是胃食道(14 [15%])、肺(12 [13%])、卵巢(11 [12%])、宫颈(11 [12%])和乳腺(9 [10%])。截至数据截止日(2023 年 4 月 30 日),部位特异性治疗组的中位随访时间为 33-3 个月(IQR 30-4-51-0),经验性化疗组的中位随访时间为 30-9 个月(27-6-35-5)。部位特异性疗法的中位无进展生存期明显长于经验性化疗(9-6 个月 [95% CI 8-4-11-9] vs 6-6 个月 [5-5-7-9];未调整危险比 0-68 [95% CI 0-49-0-93];P=0-017)。在开始计划治疗的 167 例患者中,82 例部位特异性治疗组患者中有 46 例(56%)和 85 例经验性化疗组患者中有 52 例(61%)出现了 3 级或更严重的治疗相关不良事件;在部位特异性治疗组和经验性化疗组中,最常见的不良事件是中性粒细胞计数减少(36 例 [44%] vs 42 例 [49%])、白细胞计数减少(17 例 [21%] vs 26 例 [31%])和贫血(10 例 [12%] vs 9 例 [11%])。治疗相关的严重不良事件在特定部位治疗组中有 5 例(6%),在经验性化疗组中有 2 例(2%)。未发现与治疗相关的死亡病例:这项单中心随机试验表明,与经验性化疗相比,90基因表达检测法指导的部位特异性疗法可提高既往未接受过治疗的CUP患者的无进展生存率。通过90-基因表达检测进行位点特异性预测,可为这些患者提供更多疾病信息,扩大治疗手段:基金:上海市医院发展中心临床研究计划、上海市优秀学术带头人项目、上海市抗癌协会SOAR项目:摘要中译文见补充材料部分。
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来源期刊
Lancet Oncology
Lancet Oncology 医学-肿瘤学
CiteScore
62.10
自引率
1.00%
发文量
913
审稿时长
3-8 weeks
期刊介绍: The Lancet Oncology is a trusted international journal that addresses various topics in clinical practice, health policy, and global oncology. It covers a wide range of cancer types, including breast, endocrine system, gastrointestinal, genitourinary, gynaecological, haematological, head and neck, neurooncology, paediatric, thoracic, sarcoma, and skin cancers. Additionally, it includes articles on epidemiology, cancer prevention and control, supportive care, imaging, and health-care systems. The journal has an Impact Factor of 51.1, making it the leading clinical oncology research journal worldwide. It publishes different types of articles, such as Articles, Reviews, Policy Reviews, Personal Views, Clinical Pictures, Comments, Correspondence, News, and Perspectives. The Lancet Oncology also collaborates with societies, governments, NGOs, and academic centers to publish Series and Commissions that aim to drive positive changes in clinical practice and health policy in areas of global oncology that require attention.
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