Introduction

Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution.

Methods

Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1).

Results

Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008).

Discussion

We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.

中文翻译：

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晚期实体瘤的分子谱分析。早期试验中实验性分子匹配疗法对癌症患者预后的影响：MAST 研究

介绍

分子匹配疗法彻底改变了癌症治疗。我们评估了在单个机构中应用内部定制的下一代测序面板对临床结果的改善。

方法

根据多学科分子肿瘤委员会的评估，晚期实体瘤患者被分子选择接受分子匹配治疗进入早期临床试验，而不是最佳研究人员选择。主要终点是无进展生存期 (PFS)，通过匹配治疗 (PFS2) 比先前治疗 (PFS1) 长 1.3 倍的患者的比例来评估。

结果

在总共 231 名经过分子筛查的患者中，有 87 名符合分析条件。与接受标准治疗的患者（2.76 个月；95% CI，2.14-3.91，对数秩p = 0.022）相比，接受匹配治疗的患者具有更高的中位 PFS2（6.47 个月；95% CI，2.24-14.43）。在实验组中，PFS2/PFS1 比率超过 1.3 的患者比例显着更高（0.33 vs 0.08；p = 0.008）。

讨论

我们展示了机构分子肿瘤委员会在评估定制 NGS 小组的结果中的关键作用。这个过程优化了可用疗法的选择，改善了疾病控制。需要前瞻性随机试验来证实这种方法并为扩大药物获取打开大门。