Li Ji, Zhu Jin-Xian, Zhang Yu-Xin, Li Shi-Qiang
Department of General Surgery, Chongqing Western Hospital, Chongqing 400051, P.R. China.
Oncol Lett. 2024 Feb 14;27(4):153. doi: 10.3892/ol.2024.14286. eCollection 2024 Apr.
Immune checkpoint inhibitors (ICIs) have limited efficacy in mismatch repair proficient (pMMR) or metastatic microsatellite stable (MSS) advanced or metastatic colorectal cancer (mCRC). ICIs, in conjunction with tyrosine kinase inhibitors (TKIs) possessing anti-angiogenic properties, serve as a potential strategy for circumventing the resistance exhibited by MSS or pMMR mCRC to immunotherapeutic interventions. The present study aimed to evaluate efficacy and safety of ICIs + TKIs and provide a reference for the treatment of CRC. The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to July 28, 2023. A total of 14 studies were included in qualitative and quantitative analyses, with a total of 819 patients enrolled. The Newcastle-Ottawa scale scores of the 14 cohort studies included were ≥7, indicating they were of a high quality. The objective response rate (ORR) of ICIs + TKIs was 14% [95% confidence interval (CI), 0.08-0.24; P=0.132] in patients with advanced or metastatic MSS/pMMR CRC. The disease control rate (DCR) was 65% (95% CI, 0.58-0.74; P<0.0001). The overall incidence of adverse events of varying severity linked to combination of ICIs and TKIs in patients with advanced or metastatic MSS/pMMR CRC was 64% (95% CI, 0.52-0.78; P<0.0001). The incidence of grade ≥3 adverse reactions was 24% (95% CI, 0.14-0.4; P<0.0001). The sensitivity analysis indicated that the exclusion of individual studies did not yield statistically significant variations in combined analysis results. Based on the examination of publication bias, ORR and DCR, Begg's and Egger's tests had P-values of 0.114 and 0.395, respectively. Overall publication bias overall was absent in the Begg's funnel plot, as there was no apparent asymmetry. Nonetheless, the P-values of the Egger's and Begg's tests for adverse reactions and adverse reactions grade ≥3 were P=0.008 and P=0.048, respectively. The asymmetry of the Begg's funnel plots was evident, suggesting the presence of potential publication bias regarding adverse event results. In conclusion, the combination of ICIs and TKIs demonstrates a favorable effectiveness and notable safety profile in the management of patients with advanced or metastatic MSS/pMMR CRC.
免疫检查点抑制剂（ICI）在错配修复功能正常（pMMR）或微卫星稳定（MSS）的晚期或转移性结直肠癌（mCRC）中疗效有限。ICI与具有抗血管生成特性的酪氨酸激酶抑制剂（TKI）联合使用，是一种潜在策略，可规避MSS或pMMR mCRC对免疫治疗干预的耐药性。本研究旨在评估ICI + TKI的疗效和安全性，为CRC的治疗提供参考。本系统评价和荟萃分析按照系统评价和荟萃分析的首选报告项目指南进行。检索了2003年1月1日至2023年7月28日的PubMed、Embase、Cochrane、Web of Science和ClinicalTrials.gov数据库。共纳入14项研究进行定性和定量分析，共纳入819例患者。纳入的14项队列研究的纽卡斯尔-渥太华量表评分≥7，表明它们质量较高。在晚期或转移性MSS/pMMR CRC患者中，ICI + TKI的客观缓解率（ORR）为14%[95%置信区间（CI），0.08 - 0.24；P = 0.132]。疾病控制率（DCR）为65%（95% CI，0.58 - 0.74；P < 0.0001）。晚期或转移性MSS/pMMR CRC患者中，与ICI和TKI联合使用相关的不同严重程度不良事件的总发生率为64%（95% CI，0.52 - 0.78；P < 0.0001）。≥3级不良反应的发生率为24%（95% CI，0.14 - 0.4；P < 0.0001）。敏感性分析表明，排除个别研究后，合并分析结果无统计学显著差异。基于对发表偏倚的检验，ORR和DCR的Begg检验和Egger检验的P值分别为0.114和0.395。在Begg漏斗图中总体不存在发表偏倚，因为没有明显的不对称性。然而，不良反应和≥3级不良反应的Egger检验和Begg检验的P值分别为P = 0.008和P = 0.048。Begg漏斗图的不对称性明显，表明在不良事件结果方面存在潜在的发表偏倚。总之，ICI和TKI联合使用在晚期或转移性MSS/pMMR CRC患者的治疗中显示出良好的有效性和显著的安全性。
