Vall d'Hebron Hospital Campus & Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Future Oncol. 2024 Apr;20(11):653-663. doi: 10.2217/fon-2022-1249. Epub 2023 Oct 10.
Patients with both V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination of pembrolizumab with encorafenib and cetuximab versus pembrolizumab alone in patients with previously untreated V600E-mutant, MSI-H/dMMR mCRC.
同时携带 V600E 突变和微卫星高度不稳定/错配修复缺陷（dMMR）的转移性结直肠癌（mCRC）患者预后不良。目前，对于同时携带这两种分子异常的 mCRC 患者，尚无特定的一线治疗选择。派姆单抗是一种已被批准用于治疗 MSI-H/dMMR mCRC 的检查点抑制剂，BRAF 抑制剂恩考芬尼联合西妥昔单抗已被批准用于治疗先前接受过治疗的 V600E 突变型 mCRC。派姆单抗联合恩考芬尼和西妥昔单抗可能会协同增强 V600E 突变、MSI-H/dMMR mCRC 患者的抗肿瘤活性。SEAMARK 是一项随机的 II 期研究，比较了派姆单抗联合恩考芬尼和西妥昔单抗与单独使用派姆单抗治疗未经治疗的 V600E 突变、MSI-H/dMMR mCRC 患者的疗效。
