Department of Medical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
Department of Pathology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
Oncologist. 2020 Nov;25(11):e1691-e1700. doi: 10.1634/theoncologist.2020-0274. Epub 2020 Sep 12.
Metastatic esophagogastric cancers (EGCs) have a poor prognosis with an approximately 5% 5-year survival. Additional treatment approaches are needed. c-MET gene-amplified tumors are an uncommon but potentially targetable subset of EGC. Clinical characteristics and outcomes were evaluated in patients with MET-amplified EGC and compared with those without MET amplification to facilitate identification of these patients and possible treatment approaches.
Patients with locally advanced or metastatic MET-amplified EGC at Massachusetts General Hospital (MGH) were identified using fluorescent in situ hybridization analysis, with a gene-to-control ratio of ≥2.2 defined as positive. Non-MET-amplified patients identified during the same time period who had undergone tumor genotyping and treatment at MGH were evaluated as a comparison group.
We identified 233 patients evaluated for MET amplification from 2002 to 2019. MET amplification was seen in 28 (12%) patients versus 205 (88%) patients without amplification. Most MET-amplified tumors occurred in either the distal esophagus (n = 9; 32%) or gastroesophageal junction (n = 10; 36%). Of MET-amplified patients, 16 (57%) had a TP53 mutation, 5(18%) had HER2 co-amplification, 2 (7.0%) had EGFR co-amplification, and 1 (3.5%) had FGFR2 co-amplification. MET-amplified tumors more frequently had poorly differentiated histology (19/28, 68.0% vs. 66/205, 32%; p = .02). Progression-free survival to initial treatment was substantially shorter for all MET-amplified patients (5.6 vs. 8.8 months, p = .026) and for those with metastatic disease at presentation (4.0 vs. 7.6 months, p = .01). Overall, patients with MET amplification had shorter overall survival (19.3 vs. 24.6 months, p = .049). No difference in survival was seen between low MET-amplified tumors (≥2.2 and <25 MET copy number) compared with highly amplified tumors (≥25 MET copy number).
MET-amplified EGC represents a distinct clinical entity characterized by rapid progression and short survival. Ideally, the identification of these patients will provide opportunities to participate in clinical trials in an attempt to improve outcomes.
This article describes 233 patients who received MET amplification testing and reports (a) a positivity rate of 12%, similar to the rate of HER2 positivity in this data set; (b) the clinical characteristics of poorly differentiated tumors and nodal metastases; and (c) markedly shorter progression-free survival and overall survival in MET-amplified tumors. Favorable outcomes are reported for patients treated with MET inhibitors. Given the lack of published data in MET-amplified esophagogastric cancers and the urgent clinical importance of identifying patients with MET amplification for MET-directed therapy, this large series is a valuable addition to the literature and will have an impact on future practice.
转移性胃食管癌症（EGC）预后较差，约 5%的患者 5 年生存率。需要额外的治疗方法。c-MET 基因扩增的肿瘤是 EGC 的一个罕见但潜在可靶向的亚组。评估了具有 MET 扩增的 EGC 患者的临床特征和结局，并与无 MET 扩增的患者进行了比较，以帮助识别这些患者和可能的治疗方法。
使用荧光原位杂交分析在马萨诸塞州总医院（MGH）鉴定局部晚期或转移性 MET 扩增的 EGC 患者，基因与对照的比值≥2.2 定义为阳性。同时评估在同一时期在 MGH 接受肿瘤基因分型和治疗的非 MET 扩增患者作为对照组。
我们从 2002 年到 2019 年共鉴定了 233 名接受 MET 扩增检测的患者。28 名（12%）患者的 MET 扩增，而 205 名（88%）患者无扩增。大多数 MET 扩增的肿瘤发生在远端食管（n=9；32%）或胃食管交界处（n=10；36%）。在 MET 扩增的患者中，16 名（57%）有 TP53 突变，5 名（18%）有 HER2 共扩增，2 名（7.0%）有 EGFR 共扩增，1 名（3.5%）有 FGFR2 共扩增。MET 扩增的肿瘤更常具有低分化组织学特征（19/28，68.0% vs. 66/205，32%；p=0.02）。所有 MET 扩增患者的初始治疗无进展生存期明显缩短（5.6 vs. 8.8 个月，p=0.026），且在就诊时为转移性疾病的患者生存期更短（4.0 vs. 7.6 个月，p=0.01）。总体而言，MET 扩增患者的总生存期较短（19.3 个月 vs. 24.6 个月，p=0.049）。与高 MET 扩增肿瘤（≥25 个 MET 拷贝数）相比，低 MET 扩增肿瘤（≥2.2 个和<25 个 MET 拷贝数）的生存期没有差异。
MET 扩增的 EGC 代表一种独特的临床实体，其特征为快速进展和短生存期。理想情况下，这些患者的鉴定将为他们提供参与临床试验的机会，以试图改善结局。
本文描述了 233 名接受 MET 扩增检测的患者，并报告了（a）阳性率为 12%，与该数据集的 HER2 阳性率相似；（b）低分化肿瘤和淋巴结转移的临床特征；以及（c）MET 扩增肿瘤的无进展生存期和总生存期明显缩短。报道了接受 MET 抑制剂治疗的患者的良好结局。鉴于 MET 扩增型胃食管癌症缺乏已发表的数据，以及为了识别需要 MET 靶向治疗的 MET 扩增患者的紧迫性，这项大型研究系列是文献的宝贵补充，并将对未来的实践产生影响。
