[PARPi作为新诊断上皮性卵巢癌患者一线维持治疗的真实世界临床数据分析]

[Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients].

作者信息

Wang D F, Zhang J, Zhang C, Yu J, Shi Y, Xu S Q, Fan Y, Zhou F Z, Song S Q, Liu H, Zhang G N

机构信息

Department of Gynecologic Oncology, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2022 Sep 25;57(9):641-652. doi: 10.3760/cma.j.cn112141-20220728-00490.

Abstract

The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored. (1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed. (1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all <0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95%: 25.9-33.6 months), and the median overall survival was 49.8 months (95%: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all <0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all <0.05). Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

摘要

回顾性分析新诊断卵巢癌(包括输卵管癌和原发性腹膜癌)患者接受聚腺苷二磷酸核糖聚合酶抑制剂(PARPi)一线维持治疗的真实世界临床数据,并初步探索预后因素。(1)收集2018年8月(PARPi在中国上市)至2021年12月31日在四川省肿瘤医院接受PARPi一线维持治疗的卵巢癌患者的临床病理资料及随访数据(真实世界临床数据)。(2)根据PARPi的不同类型,将真实世界临床数据分为奥拉帕利组和尼拉帕利组,分别与国内外代表性Ⅲ期随机对照试验(RCT)的纳入和排除标准进行比较,包括奥拉帕利作为BRCA1/2基因突变的晚期卵巢癌患者的一线维持治疗(SOLO-1研究)、尼拉帕利作为一线维持治疗(PRIMA研究)以及尼拉帕利作为中国晚期卵巢癌患者的一线维持治疗(PRIME研究)。(3)分析两组患者的预后情况及预后因素。(1)本研究共纳入83例患者,中位年龄51岁(47 - 57岁),其中卵巢癌75例,输卵管癌5例,原发性腹膜癌3例;Ⅰ期5例,Ⅱ期9例,Ⅲ期55例,Ⅳ期12例,分期不明2例;40例行新辅助化疗(NACT),43例未行NACT;62例术后无可见残留病灶(R0),9例残留病灶<1 cm(R1),8例残留病灶≥1 cm(R2),4例术后残留病灶情况不明。32例PARPi治疗中断,40例PARPi减量,1例因急性白血病终止治疗。83例患者中,奥拉帕利组35例,尼拉帕利组48例。奥拉帕利组高级别浆液性癌患者比例(分别为100%和75%)及BRCA突变患者比例(分别为91%和10%)高于尼拉帕利组(均<0.01)。(2)与SOLO-1研究的纳入和排除标准相比,奥拉帕利组符合率仅为60%(21/35);与PRIMA和PRIME研究的纳入和排除标准相比,尼拉帕利组符合率分别仅为31%(15/48)和69%(33/48)。不符合标准的最常见原因是化疗疗程数、组织病理学类型和手术病理分期。(3)83例接受PARPi一线维持治疗的患者中,中位随访时间为15.9个月(11.3 - 22.9个月),中位无进展生存期(PFS)为29.7个月(95%:25.9 - 33.6个月),中位总生存期为49.8个月(95%:47.4 - 52.2个月)。单因素分析显示,单侧或双侧卵巢癌、含铂化疗疗效、化疗结束时有无可测量病灶以及化疗总疗程数与PFS显著相关(均<0.05)。多因素分析显示,单侧或双侧卵巢癌、化疗总疗程数以及含铂化疗疗效是影响PARPi一线维持治疗的Ⅱ - Ⅳ期患者PFS的独立因素(均<0.05)。单侧卵巢癌、化疗总疗程数不超过9个以及维持治疗前含铂化疗达到完全缓解是PARPi一线维持治疗患者PFS获益的独立影响因素。由于真实临床实践中的患者与Ⅲ期RCT的研究对象差异较大,代表性回顾性研究结果仍具有重要的临床参考意义。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索