呋喹替尼联合PD⁃1抑制剂在晚期结直肠癌中的临床疗效和安全性

Clinical Efficacy and Safety of Fruquintinib Combined With PD⁃1 Inhibitors in Advanced Colorectal Cancer

目的评估呋喹替尼联合PD-1抑制剂在三线及以上治疗晚期结直肠癌(colorectal cancer,CRC)的疗效和安全性。方法回顾性分析2020年1月~2023年8月在某院确诊为晚期CRC并接受呋喹替尼单药或呋喹替尼联合PD-1抑制剂作为三线及以上治疗方案的93例患者。根据治疗方案分为两组,呋喹替尼单药组63例,联合组30例。分析并比较两组患者的客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、无疾病进展生存期(progression-free survival,PFS)及不良反应方面的差异。进一步研究分析两组患者的中性粒细胞淋巴细胞比值(NLR)、血小板淋巴细胞比值(PLR)、全身免疫炎症指数(SII)、预后营养指数(PNI)对患者预后的差异情况。结果联合组患者的ORR(16.7%)明显高于单药组患者的ORR(6.3%),但差异无统计学意义(χ^(2)=2.475,P=0.116)。与单药组患者相比,联合组患者的DCR(66.7%)明显更高,差异有统计学意义(χ^(2)=5.244,P=0.022)。联合组的治疗2个周期后PNI明显高于单药组,但NLR、PLR、PNI、SII均差异无统计学意义。联合组mCRC患者使用不同PD-1之间的疗效比较:CR、PR、SD、PD、ORR、DCR均差异无统计学意义。Kaplan-Meier生存分析表明联合组患者的中位PFS长于单药组患者(4.0个月比2.0个月),差异有统计学意义(χ^(2)=4.323,P=0.038)。两组患者的不良反应发生率和≥3级的不良反应发生率均差异无统计学意义。所有的患者的不良反应经过对症治疗或者停止治疗后都能得到控制和缓解,没有患者因严重的不良反应而死亡。结论在mCRC三线及以上治疗中,与呋喹替尼单药组相比,呋喹替尼联合PD-1抑制剂有更好的获益,且安全性方面可控,值得进一步开展研究。

OBJECTIVE To evaluate the efficacy and safety of fruquintinib combined with PD-1 inhibitors in the treatment of advanced colorectal cancer(CRC)in the third line and above.METHODS A retrospective analysis was performed on 93 patients diagnosed with advanced CRC who received fuquinitinib monotherapy or fuquinitinib combined with PD-1 inhibitors as third-line or higher treatment options in a hospital from January 2020 to August 2023.According to the treatment plan,the patients were divided into two groups:Fruquintinib monotherapy group(63 cases)and combined group(30 cases).Objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and adverse reactions between the two groups were analyzed and compared.The differences of neutrophil lymphocyte ratio(NLR),platelet lymphocyte ratio(PLR),systemic immunoinflammatory index(SII)and prognostic nutritional index(PNI)between the two groups were further studied and analyzed.RESULTS The ORR in the combined group(16.7%)was significantly higher than that in the monotherapy group(6.3%),but the difference was not statistically significant(χ^(2)=2.475,P=0.116).Compared with the monotherapy group,the DCR in the combination group was significantly higher(66.7%),the difference was statistically significant(χ^(2)=5.244,P=0.022).After 2 cycles of treatment,PNI in combination group was significantly higher than that in monotherapy group,but there was no statistical significance in NLR,PLR,PNI and SII.There was no significant difference in CR,PR,SD,PD,ORR and DCR among mCRC patients in the combined group using different PD-1.Kaplan-Meier survival analysis showed that the median PFS in the combination group was longer than that in the monotherapy group(4.0 months vs.2.0 months),and the difference was statistically significant(χ^(2)=4.323,P=0.038).There was no significant difference in the incidence of adverse reactions and the incidence of adverse reactions≥grade 3 between the two groups.All patients'adverse reactions were controlled and resolved after symptomatic treatment or discontinuation of treatment,and no patients died from serious adverse reactions.CONCLUSION In the third-line and above mCRC treatment,compared with the fruquintinib monotherapy group,fruquintinib combined with PD-1 inhibitor has better benefits and controllable safety,which is worthy of further research.