Introduction: Partner and localizer of BRCA2 (PALB2) is essential for homologous recombination repair. We examined mRNA levels of DNA repair genes, including partner and localizer of BRCA2 gene (PALB2), ring finger protein 8 gene (RNF8), replication timing regulatory factor 1 gene (RIF1), ATM serine/threonine kinase gene (ATM), and tumor protein p53 binding protein 1 gene (53BP1) as predictive biomarkers for cisplatin‐docetaxel in the European phase III BRCA1, DNA repair associated (BRCA1)–receptor‐associated protein 80 (RAP80) expression customization (BREC) phase III clinical trial (ClinicalTrials.gov identifier NCT00617656). Methods: The study was a prespecified secondary objective of the BREC trial. We assessed mRNA levels of PALB2 and four more DNA repair genes (RNF8, RIF1, ATM and 53BP1) as biomarkers in tissue from 177 patients with cisplatin‐docetaxel–treated NSCLC. We examined the relationship of gene expression levels with progression‐free survival, overall survival, and response. Results: In 177 patients with NSCLC (who had a median age of 62 years and included 140 men and 91 patients with adenocarcinoma), only high PALB2 mRNA expression was predictive in the progression‐free survival Cox regression analysis (hazard ratio = 0.63, 95% confidence interval: 0.42–0.83, p = 0.0080). PALB2 was also predictive of overall survival (hazard ratio = 0.68, 95% confidence interval: 0.42–0.90, p = 0.0266). Among the 158 patients evaluable for response, high PALB2 mRNA expression was predictive of response to cisplatin‐docetaxel. Specifically, an objective response rate of 77% to cisplatin‐docetaxel was observed for patients with high PALB2 mRNA expression compared with a rate of only 23 % for those with low PALB2 mRNA expression (p = 0.0448). Conclusions: High PALB2 mRNA expression identified patients with NSCLC who significantly benefited from cisplatin‐docetaxel chemotherapy in the European BREC phase III clinical trial. The combination of chemotherapy with immunotherapy will become the standard of care, and a predictive marker of response to chemotherapy may accurately guide therapeutic decision making.

中文翻译：

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简要报告：PALB2 信使 RNA 表达与铂-多西他赛治疗晚期非小细胞肺癌疗效的相关性

简介：BRCA2 (PALB2) 的伙伴和定位器对于同源重组修复至关重要。我们检查了 DNA 修复基因的 mRNA 水平，包括 BRCA2 基因 (PALB2)、环指蛋白 8 基因 (RNF8)、复制时间调节因子 1 基因 (RIF1)、ATM 丝氨酸/苏氨酸激酶基因 (ATM) 和定位器的 mRNA 水平，以及肿瘤蛋白 p53 结合蛋白 1 基因 (53BP1) 作为欧洲 III 期 BRCA1、DNA 修复相关 (BRCA1)-受体相关蛋白 80 (RAP80) 表达定制 (BREC) III 期临床试验 (ClinicalTrials) 中顺铂-多西他赛的预测生物标志物.gov 标识符 NCT00617656）。方法：该研究是 BREC 试验预设的次要目标。我们评估了 PALB2 和另外四个 DNA 修复基因（RNF8、RIF1、ATM 和 53BP1) 作为 177 名顺铂-多西他赛治疗的 NSCLC 患者组织中的生物标志物。我们检查了基因表达水平与无进展生存期、总生存期和反应的关系。结果：在 177 名 NSCLC 患者（中位年龄为 62 岁，包括 140 名男性和 91 名腺癌患者）中，只有高 PALB2 mRNA 表达在无进展生存期 Cox 回归分析中具有预测性（风险比 = 0.63, 95 % 置信区间：0.42–0.83，p = 0.0080）。PALB2 还可预测总生存期（风险比 = 0.68，95% 置信区间：0.42–0.90，p = 0.0266）。在可评估反应的 158 名患者中，高 PALB2 mRNA 表达预示着对顺铂-多西他赛的反应。具体来说，观察到 PALB2 mRNA 表达高的患者对顺铂-多西他赛的客观缓解率为 77%，而 PALB2 mRNA 表达低的患者的客观缓解率仅为 23%（p = 0.0448）。结论：高 PALB2 mRNA 表达确定了在欧洲 BREC III 期临床试验中显着受益于顺铂-多西他赛化疗的 NSCLC 患者。化疗与免疫疗法的结合将成为护理标准，对化疗反应的预测标志物可以准确地指导治疗决策。在欧洲 BREC III 期临床试验中，高 PALB2 mRNA 表达确定了从顺铂-多西他赛化疗中显着受益的非小细胞肺癌患者。化疗与免疫疗法的结合将成为护理标准，对化疗反应的预测标志物可以准确地指导治疗决策。在欧洲 BREC III 期临床试验中，高 PALB2 mRNA 表达确定了从顺铂-多西他赛化疗中显着受益的非小细胞肺癌患者。化疗与免疫疗法的结合将成为护理标准，对化疗反应的预测标志物可以准确地指导治疗决策。