Multiplatform Molecular Profiling: A Precision Medicine Victory Built on Cytotoxic Chemotherapy.
Multiplatform Molecular Profiling: A Precision Medicine Victory Built on Cytotoxic Chemotherapy.
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多平台分子分析：基于细胞毒性化疗的精准医学胜利。
DOI：
10.1097/ppo.0000000000000359
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Koschmann,Carl
中科院分区：
文献类型：
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作者：
Cantor,Evan;Koschmann,Carl
在本期《癌症杂志》中，Seeber 等人。展示他们的研究结果，将精准医学方法应用于非常困难的人群：已经接受过多种治疗的持续性癌症患者。这些患者通常将精准医疗作为最后的手段，但与之前的治疗相比，无进展生存期 (PFS) 显着增加。这项引人注目的研究是对多平台分子分析 (MMP) 的回顾性汇总分析，这是一种结合精准医学诊断的方法：下一代测序、免疫组织化学和原位杂交。该研究最终报告称，MMP 通过选择靶向治疗对患者的治疗结果有益，其中大多数决策“由免疫组织化学数据驱动，与细胞毒性治疗的预测相关。”诸如此类的研究表明了精确诊断的发展速度。本研究中患者的肿瘤接受了一系列测试，这些测试捕捉了不断变化的技术，从免疫组织化学到诊断性桑格测序，再到 46 和 592 基因组和完整的外显子覆盖。这项研究包括来自 4 项使用 MMP 的研究的汇总分析数据，MMP 被定义为“肿瘤在遗传和蛋白质水平上的表征”。在 ONCO-T-Profile 项目中，110 名没有标准治疗的实体瘤患者接受了治疗医生和专家小组选择的靶向治疗。接下来，对 28 名难治性乳腺癌患者 (Side-Out) 进行了一项多中心试点研究，他们接受了由肿瘤学家和病理学家组成的团队选择的治疗方法。该组提供了最结构化的治疗系统，优先选择多模式治疗而不是单药治疗。另外两组难治性实体瘤患者在黎巴嫩（62 名患者）和澳大利亚（54 名患者）接受了 MMP 分析，并通过肿瘤委员会更传统的讨论确定治疗方案。在 4 组的 202 名入组和分析患者中，有 166 名患者能够根据其分子特征进行评估并存活下来并接受治疗。有趣的是，这 166 例患者中超过 80% 只接受了细胞毒性化疗。在对 140 名既往非基于档案的治疗进行比较的患者中，71% 接受了单独化疗； 8%，化疗和靶向治疗； 9%，单独靶向治疗；其余的则与激素疗法相结合。作者发现，基于 MMP 的方法对 52% 的患者具有临床益处，中位无进展生存期为 180 天，而之前治疗的中位无进展生存期为 62 天。对于那些接受 MMP 帮助且没有其他可用标准疗法的患者，无进展生存期 (PFS) 中位数延长了 4 个月。作者指出，靶向治疗的 PFS 似乎比单纯化疗方案更长，但许多患者通过将生物标志物预测反应与传统化疗相结合而得到帮助。正如作者指出的，结果受到以下因素的限制：使用 4 项 MMP 方法略有不同的研究、开放标签设计的需要以及排除预期寿命为 3 个月或更短的患者。最近的一些研究已经证明了针对患者特异性肿瘤诊断的治疗的益处。最近对 570 项研究（32,149 名患者）进行的荟萃分析显示，与非个性化靶向治疗和单独的细胞毒性化疗相比，II 期个性化靶向治疗在更好的结果和更少的死亡方面具有优势。 1 此外，第一阶段肿瘤学研究的荟萃分析表明，使用生物标志物进行靶向治疗的策略是……
In this issue of The Cancer Journal, Seeber et al. present their findings applying precision medicine methodologies to a very difficult population: patients with persistent cancer who have already received multiple therapies. These are patients turning to precision medicine often as a last resort, and yet progressionfree survival (PFS) was significantly increased compared with prior therapy. This compelling study is a retrospective pooled analysis of multiplatform molecular profiling (MMP), an approach utilizing a combination of precision medicine diagnostics: next-generation sequencing, immunohistochemistry, and in situ hybridization. The study ultimately reports MMP to be beneficial for patient outcome through the selection of targeted therapies, with the majority of decisions “driven by immunohistochemistry data with predictive associations for cytotoxic treatments.” Studies such as this one demonstrate the pace at which precision diagnostics are evolving. The patients' tumors in this study underwent a range of tests that capture the changing technology, from immunohistochemistry to diagnostic Sanger sequencing to 46 and 592 gene panels and full exon coverage. This study includes pooled-analysis data from 4 studies that used MMP, defined as “a characterization of tumors on the genetic and protein level.” In the ONCO-T-Profile project, 110 patients with solid tumors and no standard treatment available underwent targeted therapies selected by treating physicians as well as an expert panel. Next, a multicenter pilot study of 28 refractory breast cancer patients (Side-Out) underwent treatments selected by a team of oncologists and pathologists. This group provided the most structured system of treatment, with preference for multimodal instead of single-agent therapy. Two additional cohorts of refractory solid tumor patients underwent MMP profiling in Lebanon (62 patients) and Australia (54 patients) and had treatment determined by more traditional discussion at tumor boards. Of the 202 enrolled and profiled patients between the 4 groups, 166 were able to be evaluated and survived to receive treatment based on their molecular profile. Interestingly, more than 80% of those 166 were treated with cytotoxic chemotherapy alone. Of the 140 patients with comparison of prior non–profile-based treatment, 71% received chemotherapy alone; 8%, chemotherapy and targeted therapy; 9%, targeted therapy alone; and the rest, a combination with hormone therapy. The authors found that the MMP-based approach had a clinical benefit for 52% of patients, with 180 days of median PFS versus 62 days on their prior treatment. For those helped by MMP and with no other standard therapies available, there was a median of 4 months added PFS. The authors note that PFS appeared longer with targeted therapy than chemotherapy-based regimens alone, but that many patients were helped by the integration of biomarkers predication response to conventional chemotherapy. As the authors point out, the results are limited by the use of 4 studies with slightly different approaches to MMP, the need for open-label design, and its exclusion of patients with a life expectancy of 3 months or less.A number of recent studies have demonstrated the benefit of therapy targeted to patient-specific tumor diagnostics. A recent meta-analysis of 570 studies (32,149 patients) showed a benefit of phase II personalized targeted therapies compared with nonpersonalized targeted therapies and cytotoxic chemotherapy alone, in terms of better outcomes and fewer deaths. 1 Additionally, a meta-analysis of stage 1 oncology studies demonstrated that strategies using biomarkers to target therapy were …