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

Objective: 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. Methods: (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. Results: (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 P<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%CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95%CI: 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 P<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 P<0.05). Conclusions: 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.目的： 回顾性分析初治卵巢上皮性癌（卵巢癌；包括输卵管癌和原发性腹膜癌）患者行聚二磷酸腺苷核糖聚合酶抑制剂（PARPi）一线维持治疗的真实世界临床数据，并对预后相关影响因素进行初步探索。 方法： （1）收集自2018年8月（PARPi国内上市）至2021年12月31日在四川省肿瘤医院就诊行PARPi一线维持治疗的卵巢癌患者的临床病理资料及随访资料（即本研究的真实世界临床数据）。（2）根据PARPi种类不同将本研究的真实世界临床数据分为奥拉帕利组和尼拉帕利组，分别与具有代表性的国内外Ⅲ期随机对照试验（RCT），包括BRCA1/2基因突变的晚期卵巢癌奥拉帕利单药一线维持治疗（即SOLO-1研究）、卵巢癌尼拉帕利单药一线维持治疗（即PRIMA研究）、针对中国人群的晚期卵巢癌尼拉帕利一线维持治疗（即PRIME研究）的研究对象入排标准进行对比。（3）分析本研究的真实世界临床数据中两组卵巢癌患者的预后，并对影响预后的相关因素进行单因素和多因素分析。 结果： （1）本研究的真实世界临床实践中，纳入行PARPi一线维持治疗的卵巢癌患者共83例，其中位年龄为51岁（47~57岁）。83例患者中，卵巢癌75例、输卵管癌5例、原发性腹膜癌3例；手术病理分期：Ⅰ期5例，Ⅱ期9例，Ⅲ期55例，Ⅳ期12例，不详2例；新辅助化疗（NACT）：有NACT者40例，无NACT者43例；术后无肉眼可见残留灶（R0）62例，残留灶<1 cm（R1）9例，残留灶≥1 cm（R2）8例，不详4例。PARPi治疗过程中，32例中断，40例减量，1例终止（因急性白血病终止治疗）。83例卵巢癌患者中，奥拉帕利组35例、尼拉帕利组48例，两组患者的病理类型（高级别卵巢浆液性癌占比分别为100%、75%）及BRCA基因状态（BRCA基因突变型占比分别为91%、10%）分别比较，差异均有统计学意义（P均<0.01）。（2）与SOLO-1研究的入排标准比较，本研究真实世界临床数据中的奥拉帕利组仅有60%（21/35）的符合率；与PRIMA研究、PRIME研究的入排标准比较，本研究真实世界临床数据中的尼拉帕利组仅分别有31%（15/48）和69%（33/48）的符合率。常见的不符合原因包括化疗疗程数、病理类型和手术病理分期。（3）本研究的真实世界临床数据中，行PARPi一线维持治疗的83例卵巢癌患者的中位随访时间为15.9个月（11.3~22.9个月），中位无进展生存时间（PFS）为29.7个月（95%CI为25.9~33.6个月），中位总生存时间为49.8个月（95%CI为47.4~52.2个月）。单因素分析显示，单双侧卵巢病变、总化疗疗程数、含铂化疗疗效、化疗结束时有无可测量病灶与行PARPi一线维持治疗的Ⅱ~Ⅳ期卵巢癌患者的PFS均显著相关（P均<0.05）；多因素分析显示，单双侧卵巢病变、总化疗疗程数、含铂化疗疗效是影响行PARPi一线维持治疗的Ⅱ~Ⅳ期卵巢癌患者PFS的独立因素（P均<0.05）。 结论： 本研究的真实世界临床实践中，单侧卵巢癌、总化疗疗程数<9个、含铂化疗后达到完全缓解是行PARPi一线维持治疗的卵巢癌患者PFS获益的独立影响因素；因本研究的真实世界临床实践中的患者情况与国内外Ⅲ期RCT研究的入排标准存在较大差异，故具有代表性的回顾性研究结果仍具有重要的临床参考意义。.