Nakajima Satoru, Sasaki Akinori, Okamoto Risa
Gastroenterology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, JPN.
Cureus. 2025 Jun 13;17(6):e85954. doi: 10.7759/cureus.85954. eCollection 2025 Jun.
Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy in tumor mutational burden-high (TMB-H) solid tumors and has been approved for the treatment of these diseases. Following immune checkpoint inhibitor administration, rapid tumor progression, known as hyperprogressive disease (HPD), has been observed. This report presents the case of a 60-year-old woman diagnosed with mesenchymal-epithelial transition (MET) amplification and TMB-H colorectal cancer. The patient was initially administered chemotherapy for MET amplification in a clinical trial but was considered refractory following one treatment cycle. Subsequently, she was treated with pembrolizumab for the TMB-H solid tumor. However, she developed HPD one month after starting pembrolizumab treatment and later died in the hospital. To the best of our knowledge, this is the first report of HPD in a patient with colorectal cancer harboring both MET amplification and TMB-H. It suggests that MET amplification may be involved in HPD development. These findings underscore the need for vigilance regarding HPD risk when selecting immune checkpoint inhibitor candidates and highlight the importance of future research, such as exploring MET-targeted combination strategies, in the optimization of treatment outcomes.
帕博利珠单抗是一种免疫检查点抑制剂，已在肿瘤突变负荷高（TMB-H）的实体瘤中显示出疗效，并已获批用于治疗这些疾病。在使用免疫检查点抑制剂后，已观察到快速肿瘤进展，即所谓的超进展性疾病（HPD）。本报告介绍了一例60岁女性患者，诊断为间充质-上皮转化（MET）扩增和TMB-H的结直肠癌。该患者最初在一项临床试验中因MET扩增接受化疗，但在一个治疗周期后被认为难治。随后，她因TMB-H实体瘤接受帕博利珠单抗治疗。然而，她在开始帕博利珠单抗治疗一个月后出现HPD，后来在医院死亡。据我们所知，这是首例同时存在MET扩增和TMB-H的结直肠癌患者发生HPD的报告。这表明MET扩增可能与HPD的发生有关。这些发现强调了在选择免疫检查点抑制剂候选者时对HPD风险保持警惕的必要性，并突出了未来研究的重要性，例如探索MET靶向联合策略以优化治疗结果。
