安罗替尼联合尼拉帕利治疗铂耐药复发性卵巢癌的疗效及安全性分析

The efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant recurrent ovarian cancer

目的探讨安罗替尼联合尼拉帕利治疗铂耐药复发卵巢癌的有效性和安全性。方法选取2019年9月至2021年10月中国医学科学院肿瘤医院深圳医院收治的35例铂耐药复发卵巢癌患者,既往接受过二线及以上化疗。所有患者均给予安罗替尼联合尼拉帕利治疗,主要观察终点为无进展生存时间(PFS),次要观察指标为总生存时间(OS)、客观有效率(ORR)、疾病控制率(DCR)及安全性。生存分析采用Kaplan-Meier法和Log rank检验,影响因素分析采用Cox比例风险回归模型。结果35例接受治疗的患者中,部分缓解14例,病情稳定13例,疾病进展8例,ORR为40.0%(95%CI:22.9%~57.1%),DCR为77.1%(95%CI:62.9%~91.4%)。中位随访时间为18.9个月(6.9~32.2个月),中位PFS为6.5个月(95%CI:5.4~7.7个月),中位OS为18.4个月(95%CI:16.1~20.8个月)。多因素回归分析结果提示,美国东部肿瘤协作组功能状态评分、国际妇产科联盟分期、乳腺癌易感基因(BRCA)突变是PFS的独立影响因素(均P<0.05)。首次接受PARP抑制剂治疗含BRCA突变的患者PFS(15.0个月)较未接受过PARP抑制剂治疗且不含BRCA突变的患者长(6.0个月,P=0.029)。常见的治疗相关不良反应为乏力(85.7%,30/35)、骨髓抑制(85.7%,30/35)及高血压(74.3%,26/35)。结论安罗替尼联合尼拉帕利治疗能延长铂耐药复发卵巢癌患者的生存时间,且安全性可控。

Objectives To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer.Methods Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible.All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021.The primary endpoint was progression-free survival(PFS).The second endpoints included overall survival,objective response rate(ORR),disease control rate(DCR)and safety.Survival analysis was performed using the Kaplan-Meier method and Log-rank test,and influence factor analysis was performed using Cox proportional risk regression models.Results The best overall response showed that partial response was observed in 14 patients,stable disease was noted within 13 patients,and progressive disease was found in 8 patients.Therefore,the ORR and DCR of these 35 patients were 40.0%(95%CI:22.9%-57.1%)and 77.1%(95%CI:62.9%-91.4%),respectively.The median follow-up duration was 18.9 months(6.9-32.2).The median PFS was 6.5 months(95%CI:5.35-7.66).Multivariate Cox regression analysis for PFS indicated that age,Eastern Cooperative Oncology Group performance status(ECOG PS)score,International Federation of Gynecology and Obstetrics(FIGO)stage,and BRCA mutation status were independent factors influencing PFS(P<0.05).Additionally,the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment(15.0 vs 6.0 month,P=0.029).The most common treatment-related adverse reactions were fatigue(85.7%),hematologic toxic(85.7%)and hypertension(74.3%).There were no treatment-related deaths.Conclusion Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.