彭布罗利珠单抗
微卫星不稳定性
结直肠癌
癌症
癌症研究
免疫检查点
医学
突变
肿瘤科
内科学
生物
免疫疗法
微卫星
遗传学
基因
等位基因
作者
Charan Thej Reddy Vegivinti,Cyndi Gonzales Gomez,Masood Pasha Syed,Morgan Ferrell,Svea Cheng,Aatur D. Singhi,Anwaar Saeed,İbrahim Halil Şahin
标识
DOI:10.1080/14712598.2023.2226327
摘要
The US Food and Drug Administration (FDA) approved pembrolizumab for patients with unresectable or metastatic solid tumors with tumor mutational burden (TMB) of ≥ 10 mutations/megabase. However, the clinical implications of this universal cutoff of TMB ≥ 10 for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) remain debatable.In this review, we discuss the tissue agnostic approval of pembrolizumab, its efficacy, and clinical relevance in the management of patients with MSS CRC patients with high TMB (defined as TMB ≥ 10). We also elaborate on molecular subgroups of MSS CRC that influence the immune checkpoint inhibitor (ICI) response for patients with MSS CRC, including pathogenic POLE and POLD1 mutations associated with ultramutated tumors.Patients with microsatellite stable CRC with TMB ≥ 10 without POLE and POLD1 mutations may not significantly benefit from immune checkpoint inhibitors therapy. Predetermined cutoff TMB ≥ 10 mutation per MB does not seem to define a universal cutoff for the benefit of disease-agnostic ICI therapy, particularly for patients with MSS CRC. Patients with POLE/POLD1 mutations with MSS CRC represent a unique biological subgroup of MSS CRC with favorable responses to ICI therapy.
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