阿帕替尼联合PD-1单抗后线治疗晚期结直肠癌患者的疗效和安全性

Efficacy and safety of apatinib plus PD-1 blockades as subsequent line therapy for patients with advanced colorectal cancer

目的探讨阿帕替尼联合PD-1单抗在标准方案治疗失败的晚期结直肠癌(colorectal cancer,CRC)中的疗效安全性及预后影响因素分析。方法研究设计为回顾性分析,纳入43例临床上后线接受阿帕替尼联合PD-1单抗联合治疗的晚期CRC患者。阿帕替尼用药剂量为250 mg或500 mg,PD-1单抗为已经在中国获批的PD-1单抗。通过医院电子病历系统整理患者接受治疗后的疗效及安全性数据,并对患者进行定期的随访获取长期生存的数据。此外,进行无进展生存期(PFS)和基线亚组资料的关联分析探讨影响预后的风险因素。结果最佳的疗效评估结果表明部分缓解患者11例,疾病稳定患者20例,疾病进展患者12例。因此,阿帕替尼联合PD-1单抗后线治疗晚期CRC患者的客观缓解率(ORR)为25.6%[95%置信区间(CI):13.5%~41.2%],疾病控制率(DCR)为72.1%(95%CI:56.3%~84.7%)。通过后续的访视获取的预后数据表明43例晚期CRC患者的中位PFS为5.8个月(95%CI:3.81~7.79),中位OS为10.3个月(95%CI:5.75~14.85)。最常见的不良反应分别有乏力、高血压、腹泻和手足综合征等。PFS的影响因素分析提示ECOG评分和左右半结直肠癌可能是预测患者PFS的独立影响因素。结论阿帕替尼联合PD-1单抗后线治疗晚期CRC患者具有潜在的疗效和可控的安全性。ECOG评分和肿瘤部位可能是影响患者PFS的潜在风险因素。研究结论尚需要大样本临床研究进一步验证。

Objective To investigate the efficacy and safety of apatinib combined with PD-1 blockades for patients with advanced colorectal cancer(CRC)who failed in the therapy with the standard regimens and explored the potential prognostic factors.Methods In this retrospective study,a total of 43 patients with advanced CRC who were treated with apatinib plus PD-1 blockades were included in this study.The initial dosage of apatinib was250 mg or 500 mg,and PD-1 blockades were the available PD-1 inhibitors approved in China.The data on the efficacy and safety were collected using the electronic medical record system of the hospital and all the patients were followed up regularly to assess the long-term prognostic data.Association analysis between progression free survival(PFS)and baseline characteristic subgroups was performed to explore the potential risk factors for prognosis.Results The best overall response of the combination regimen indicated that partial response was observed in 11patients,the disease was noted stable in 20 patients and progressive 12 patients,yielding an objective response rate(ORR)of 25.6%(95%CI:13.5%~41.2%)and a disease control rate(DCR)of 72.1%(95%CI:56.3%~84.7%).Furthermore,the prognostic data obtained from the subsequent follow-up suggested that the median PFS of the 43 patients was 5.8 months(95%CI:3.81~7.79)and the median overall survival(OS)was 10.3 months(95%CI:5.75~14.85).The most common adverse reactions were fatigue,hypertension,diarrhea and hand-foot syndrome.Furthermore,the association analysis suggested that ECOG performance status and left-and right-side colorectal cancer might be independent factors to predict the PFS.Conclusion The regimen of apatinib plus PD-1blockades is potential in efficacy and acceptable in safety for patients with advanced CRC in subsequent-line therapy.ECOG performance status and tumor location might be potential risk factors to predict the PFS.The conclusion should be confirmed in prospective clinical trials subsequently.