Introduction

Non-small-cell lung cancer (NSCLC) is one of the most common and deadly cancers. Several molecular drivers of oncogene addiction are now known to be strong predictive biomarkers for target therapies. Advances in large Next Generation Sequencing (LNGS) have improved the ability to detect potentially targetable mutations. However, the integration of LNGS into clinical management in an individualized manner remains challenging.

Methods

In this single-center observational study we included all patients with advanced NSCLC who underwent LNGS. Somatic and germline exome analysis was performed with a restriction on 323 cancer related genes. Variants were classified and Molecular Tumour Board (MTB) made therapeutic propositions.

Results

We performed LNGS analysis in 281 patients with advanced NSCLC between March 2015 and January 2018. Technical failure occurred in only 3% of cases. Three hundred and fifty-six targetable mutations were detected. At least one targetable mutation was found in 209 patients. For all these patients, the MTB was able to recommend treatment with a targeted agent based on the evaluation of the tumour’s genetic profile and treatment history. Twenty-nine patients (13.9%) were subsequently treated with an MTB-recommended targeted therapy. We did not observe any improvement in terms of clinical benefit for these patients.

Conclusions

In this case series, we show that including LNGS into routine clinical management was feasible but does not appear to provide clinical benefit in the management of patients with advanced NSCLC.

中文翻译：

---

使用外显子组肿瘤测序分析的大型 NGS 面板是否可以改善晚期非小细胞肺癌的管理？

介绍

非小细胞肺癌 (NSCLC) 是最常见和致命的癌症之一。现在已知几种致癌基因成瘾的分子驱动因素是靶向治疗的强大预测生物标志物。大型下一代测序 (LNGS) 的进步提高了检测潜在可靶向突变的能力。然而，以个性化的方式将 LNGS 整合到临床管理中仍然具有挑战性。

方法

在这项单中心观察性研究中，我们纳入了所有接受 LNGS 的晚期 NSCLC 患者。在限制 323 个癌症相关基因的情况下进行体细胞和种系外显子组分析。对变体进行分类，分子肿瘤委员会 (MTB) 提出了治疗建议。

结果

我们在 2015 年 3 月至 2018 年 1 月期间对 281 名晚期 NSCLC 患者进行了 LNGS 分析。仅 3% 的病例发生了技术故障。检测到 356 个可靶向突变。在 209 名患者中至少发现了一种可靶向突变。对于所有这些患者，MTB 能够根据对肿瘤遗传特征和治疗史的评估推荐使用靶向药物进行治疗。29 名患者 (13.9%) 随后接受了 MTB 推荐的靶向治疗。我们没有观察到这些患者在临床获益方面有任何改善。

结论

在这个病例系列中，我们表明将 LNGS 纳入常规临床管理是可行的，但似乎不会为晚期 NSCLC 患者的管理提供临床益处。