Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Lung Cancer. 2019 Aug;134:167-173. doi: 10.1016/j.lungcan.2019.06.017. Epub 2019 Jun 17.
Chemotherapy remains a cornerstone treatment in non-small cell lung cancer either in combination with checkpoint inhibitors or as subsequent therapy. Identifying molecular predictors of response allows for optimal treatment selection. We performed genomic analysis on tumor samples of patients treated with carboplatin and nab-paclitaxel as part of a phase II trial to evaluate the prognostic and predictive value of mutations in DNA repair pathway in patients treated with this regimen.
Next-generation sequencing libraries were produced using a capture-based targeted panel covering the coding exons of 278 genes on patients treated on clinical trial NCT00729612. Overall survival (OS) and progression-free survival (PFS) were assessed as part of the clinical outcomes and correlated with mutation analysis.
Of 63 patients enrolled, 25 patients had sufficient and acceptable DNA isolated from archival tumor samples for targeted sequencing. The most commonly altered pathways included DNA repair (DR) including Fanconi anemia and homologous recombination, JAK-STAT signaling, IGF-1, mTOR, and MAPK-ERK. Four patients with mutations in homologous recombination mutations had a shorter PFS (hazard ratio [HR] = 4.54, 95% CI 1.2, 17.1, p = 0.026) and OS (HR = 6.3, 95% CI 1.8, 21.3, p = 0.003).
In this analysis of patients with predominantly squamous cell non-small cell lung cancer treated with carboplatin and nab-paclitaxel in a phase II trial, patients with mutations in homologous recombination pathways had shorter overall and progression-free survival. Validation on additional datasets of patients treated with platinum-based chemotherapy and immunotherapy combinations is warranted.
化疗仍然是非小细胞肺癌的基石治疗方法，无论是与检查点抑制剂联合使用还是作为后续治疗。确定反应的分子预测因子可以实现最佳的治疗选择。我们对接受卡铂和nab-紫杉醇治疗的患者的肿瘤样本进行了基因组分析，这是一项 II 期试验的一部分，旨在评估该方案治疗的患者中 DNA 修复途径突变的预后和预测价值。
使用基于捕获的靶向面板在临床试验 NCT00729612 中对患者进行治疗，生成了下一代测序文库。总生存期（OS）和无进展生存期（PFS）作为临床结果的一部分进行评估，并与突变分析相关联。
在入组的 63 名患者中，有 25 名患者从存档的肿瘤样本中获得了足够且可接受的 DNA 进行靶向测序。最常改变的途径包括 DNA 修复（DR），包括范可尼贫血和同源重组、JAK-STAT 信号传导、IGF-1、mTOR 和 MAPK-ERK。4 名具有同源重组突变的患者 PFS（风险比[HR] = 4.54，95%CI 1.2，17.1，p = 0.026）和 OS（HR = 6.3，95%CI 1.8，21.3，p = 0.003）更短。
在这项对接受卡铂和 nab-紫杉醇治疗的 II 期试验中以鳞状非小细胞肺癌为主的患者的分析中，同源重组途径突变的患者总生存期和无进展生存期更短。需要在接受铂类化疗和免疫治疗联合治疗的患者的其他数据集上进行验证。
