Fakih Marwan, Sandhu Jaideep, Li Xiaochen, Wang Chongkai
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United States.
Division of Biostatistics, Department of Computational and Quantitative Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA, United States.
Oncologist. 2024 Dec 6;29(12):1052-1058. doi: 10.1093/oncolo/oyae249.
There have been conflicting reports on the predictive impact of metastatic disease sites on the response to checkpoint inhibitors (CPI) in microsatellite instability (MSI) metastatic colorectal cancers (mCRC). Recent studies have highlighted peritoneal metastases, ascites, and liver metastases as possible indicators of resistance to CPI.
We performed a detailed analysis of high microsatellite instability (MSI-H) mCRC treated with programmed cell death (PD-1) or PD-1/cytotoxic T-lymphocyte-associated protein 4 CPI in a single center. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and stable disease but with complete pathological response upon resection (SDcPR) were analyzed by the presence of liver metastases, peritoneal metastases, or absence of either. The impact of number and size of liver metastases on clinical outcomes were also interrogated.
Thirty-five patients with MSI mCRC were included in the analysis. Patients with peritoneal metastatic disease had lower ORR and shorter PFS compared to patients without liver and peritoneal metastases. Contrary to recent reports, ORR and ORR + SDcPR rates were high in patients with liver metastases, at 58% and 66%, respectively. In the liver metastases category, a better response rate was noted for patients with<5 lesions compared to patients with more than 5 lesions. Patients who responded had a higher median tumor mutation burden than patients with progressive disease.
In MSI mCRC, no single clinical characteristic was sufficient to preclude CPI response. Peritoneal metastatic disease was associated with numerically lower ORR and shorter PFS. In contrast, liver metastases do not predict poor outcome.
关于微卫星不稳定（MSI）转移性结直肠癌（mCRC）中转移病灶部位对检查点抑制剂（CPI）反应的预测影响，一直存在相互矛盾的报道。最近的研究强调腹膜转移、腹水和肝转移可能是对CPI耐药的指标。
我们在单中心对接受程序性细胞死亡蛋白1（PD-1）或PD-1/细胞毒性T淋巴细胞相关蛋白4 CPI治疗的高度微卫星不稳定（MSI-H）mCRC进行了详细分析。根据是否存在肝转移、腹膜转移或两者均无，分析总缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）以及疾病稳定但切除后有完全病理缓解（SDcPR）的情况。还探讨了肝转移的数量和大小对临床结局的影响。
35例MSI mCRC患者纳入分析。与无肝转移和腹膜转移的患者相比，有腹膜转移疾病的患者ORR较低，PFS较短。与最近的报道相反，肝转移患者的ORR和ORR + SDcPR率较高，分别为58%和66%。在肝转移组中，与病灶数超过5个的患者相比，病灶数<5个的患者缓解率更高。缓解的患者比疾病进展的患者具有更高的中位肿瘤突变负荷。
在MSI mCRC中，没有单一临床特征足以排除对CPI的反应。腹膜转移疾病与较低的ORR和较短的PFS相关。相比之下，肝转移并不能预测不良结局。
