To the Editor A recent study published in JAMA Oncology evaluated the effect of the MET inhibitor onartuzumab in combination with standard first-line chemotherapy in patients with advanced human epidermal growth factor receptor 2–negative, mesenchymal-epithelial transition (MET)–positive gastroesophageal carcinoma.¹ MET positivity was defined as at least 50% of cells staining positive with intensity of 1+ or greater. This randomized phase 3 trial was stopped early because no improvement in progression-free survival, overall survival, or overall response rate was seen in the arm treated with chemotherapy and onartuzumab, irrespective of MET expression status. These negative results are in line with previously published phase 2/3 trials showing disappointing results with MET-inhibiting drugs.² In their Discussion, Shah et al¹ describe several hypotheses to explain the failure of MET inhibitors, more specifically MET overexpression not being the appropriate target or MET signaling being a consequence rather than the cause of tumor growth, concluding that better predictive biomarkers are needed.

致编辑最近发表在JAMA Oncology上的一项研究评估了 MET 抑制剂 onartuzumab 联合标准一线化疗对晚期人类表皮生长因子受体 2 阴性、间充质-上皮转化 (MET) 阳性胃食管癌患者的影响. ¹MET 阳性定义为至少 50% 的细胞染色呈阳性，强度为 1+ 或更高。这项随机 3 期试验提前停止，因为无论 MET 表达状态如何，在接受化疗和 onartuzumab 治疗的手臂中均未观察到无进展生存期、总生存期或总缓解率的改善。这些阴性结果与先前发表的 2/3 期试验一致，该试验显示 MET 抑制药物的结果令人失望。²在他们的讨论中，Shah 等人¹描述了几个假设来解释 MET 抑制剂的失败，更具体地说，MET 过表达不是合适的靶标或 MET 信号传导是结果而不是肿瘤生长的原因，得出的结论是需要更好的预测性生物标志物.