1 Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
2 Kansai Medical University Hospital, Hirakata, Japan.
J Clin Oncol. 2019 Mar 1;37(7):570-579. doi: 10.1200/JCO.18.00771. Epub 2019 Jan 17.
Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP.
Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate.
One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types.
Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.
尽管基因表达谱分析是一种很有前途的诊断技术，可以确定癌症原发灶不明（CUP）患者的组织来源，但目前还没有临床试验评估过这种方法指导的靶向治疗与经验性化疗相比的效果。因此，我们进行了一项随机研究，以评估与经验性紫杉醇联合卡铂（PC）化疗相比，这种靶向治疗是否能改善未经治疗的 CUP 患者的预后。
通过微阵列分析进行全面的基因表达谱分析，并应用已建立的算法预测肿瘤起源。CUP 患者被随机分配（1:1）接受标准靶向治疗或经验性紫杉醇加卡铂（PC）治疗。主要终点是 1 年生存率。
130 例患者被随机分配，并进行了足够的组织学分析。对靶向治疗组和经验性 PC 组分别有 50 例和 51 例患者进行了疗效分析。最常预测的癌症类型是胰腺癌（21%）、胃癌（21%）和淋巴瘤（20%）。靶向治疗组和经验性 PC 组的 1 年生存率分别为 44.0%和 54.9%（P=0.264）。中位总生存期和无进展生存期分别为靶向治疗组 9.8 个月和 5.1 个月，经验性 PC 组为 12.5 个月和 4.8 个月（P=0.896 和 0.550）。预测更敏感肿瘤类型的中位总生存期（16.7 比 10.6 个月；P=0.116）和无进展生存期（5.5 比 3.9 个月；P=0.018）均优于预测不敏感肿瘤类型。
基于微阵列分析的靶向治疗并未显著提高 1 年生存率，与经验性 PC 相比，尽管对原始部位的预测似乎具有预后价值。
