The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China

The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China Jing Ni, Xianzhong Cheng, Qian Zhao, Zhiqin Dai, Xia Xu, Wenwen Guo, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-101839/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 May, 2021 Read the published version in Journal of Ovarian Research → Version 1 posted 11 You are reading this latest preprint version Abstract Background Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD) positive. We present real-world experience from China. Methods Patients with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx ® ) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. Results Twenty-two patients all received niraparib at an bolus of 200mg/d. 50% of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in the exploratory multi-line monotherapy group. Commonly AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. Conclusion  It is feasible for patients received a bolus of 200mg/d in Chinese population with promising efficacy and well tolerated. This is first real world data about niraparib in ovarian cancer patients with HRD status from China. Sexual & Reproductive Medicine Cancer Biology Advanced ovarian cancer Niraparib Real World Efficacy Safety HRD Figures Figure 1 Figure 2 Background Ovarian cancer is the most lethal gynecological malignancy, 70% of the patients are diagnosed with advanced stage. Although most ovarian cancer patients are sensitive to standard first-line treatment including cytoreductive surgery and platinum-based chemotherapy, about 80% patients relapse within 1 to 2 years after initial treatment and gradually progress to platinum-resistance ovarian cancer, accompanied by significantly shortened survival[1,2]. How to prolong the platinum free interval (PFI) becomes one of the breakthrough points in ovarian cancer treatment. Recently, poly ADP-ribose Polymerase (PARP) inhibitors have changed the treatment paradigm for ovarian cancer that can significantly improve the platinum free interval, and finally prolong the overall survival of patients with BRCA mutation [3-6]. PARP is a specific DNA fracture receptor, which is activated after DNA damage, recognizes and binds to the DNA fracture site, and mediates DNA single-strand damage repair in tumor cells[7]. PARP inhibitor can lead to DNA double strand damage inducing by amount of DNA single-strand damage. In homologous recombination deficiency (HRD) tumor cells, such as BRCA mutation or other germline mutations in homologous recombination repair (HRR) pathway genes (e.g., RAD51 and ATM), can not repair DNA single-strand damage, forming the synthetic lethal effect[8]. Therefore, BRCAmt or HRD positive tumor cells are more sensitive to PARP inhibitors in terms of molecular mechanisms. Niraparib (Zejula ® ), is a highly selective inhibitor of PARP1/2, nuclear proteins that detect DNA damage and promote its repair[9]. In 2017, it was firstly approved for second-line maintenance treatment of ovarian cancer patients who were in complete or partial response to platinum-based chemotherapy by Food and Drug Administration (FDA) according to the study of NOVA[3,10]. Another study observed the significant efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after response to first-line platinum-based chemotherapy[5]. Both of the NOVA and PRIMA studies found that patients with HRD positive can get more profit from niraparib. Recently the first fully powered, multi-center, phase III clinical study in Chinese population (NORA) showed that median PFS was significantly longer for niraparib as second-line maintenance treatment versus placebo among patients with germline BRCA mutations (not reached vs. 5.5 months; HR was 0.22) and those without germline BRCA mutations (11.1 vs. 3.9 months; HR was 0.40) in 2020 ESMO meeting[11]. QUADRA study demonstrated that niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which included not only patients with BRCA mutation but also population with BRCA wild-type [12]. However, there was no real-world data to illustrate the efficacy and safety of niraparib in Chinese population. We conducted this study to assess the real-world clinical impact of niraparib in ovarian cancer patients with HRD status. Materials And Methods Study population Patients with advanced ovarian cancer who received niraparib from June 2019 to July 2020 were included in Jiangsu Cancer Hospital. We collected the basic characteristics of these patients, including age, Eastern Cooperative Oncology Group performance status (ECOG PS) before the start of the treatment, histological type, clinical stage on the basis of Federation International of Gynecology and Obstetrics (FIGO), basal body weight, basal platelet count, previous therapy before and after the treatment of niraparib and the follow-up. The study was approved by the ethics committee of Jiangsu Cancer Hospital. Dosing Regimen The initial dose was base on the level of basal body weight or platelet count. Patients with basal body weight ≥77kg and basal platelet count of ≥150,000/microliter (μL) will take 300 mg daily. While patients with basal body weight<77 kg and/or basal platelet count<150,000/μLwill take 200 mg daily. Dose reduction (300mg to 200mg or 100mg; 200mg to 100mg) or interruption for drug-related AEs was allowed. Serum CA125 and imaging examinations were performed on each patient at baseline, followed by a monthly examination of CA125 and imaging examinations. HRD testing The paraffin sections from the cytoreductive surgery were obtained after patients’ informed consent. DNA was extracted from FFPE biopsy/surgical specimens; 50 to 200 ng DNA undergoes library construction and hybrid capture with AmoyDx ® HRD panel, which selected coding sequences (CDS) regions for 54 HRR pathway genes and 72000 single nucleotide polymorphisms (SNPs) for HRD calling. The selected libraries were pooled and sequenced on the Illumina Novaseq6000 to >500× unique coverage for 54 HRR genes and >100× for SNP loci. Sequence data was processed using a customized analysis pipeline designed to accurately detect multiple classes of genomic alterations: base substitutions, short insertions/deletions with detection sensitivity at variant allele frequency (VAF) ≥5%. Detected mutations were annotated according to American College of Medical Genetics (ACMG) guideline[13] and classified as pathogenic, likely pathogenic, variants of unknown significance, likely benign and benign. HRD score was calculated by the sum of three types of genomic instable events including loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transition (LST) defined by ref[14]. HRD-positive was defined by either BRCA1/2 pathogenic or likely pathogenic mutation or HRD score ≥42. Assessments Demographic and baseline data were summarized and analyzed. The efficacy was assessed as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) by RECIST 1.1. Objective response rate (ORR) was defined as the proportion of patients achieving CR or PR. Disease control rate (DCR) was defined as the proportion of patients achieving CR, PR or SD for at least 8 weeks. Treatment-related adverse events (AEs) were graded according to CTCAE 5.0. Statistical analysis The 95% confidence interval was calculated using the Wilson procedure with a correction for continuity. Data were statistically analyzed using SPSS version 19.0 professional statistical software and all the count data were expressed as a percentage (%). Results Patients’ characteristics A total of twenty-two patients treated with niraparib were enrolled, of whom twenty-one patients were ovary cancer and one patient was fallopian tube cancer. The median age was 55.0 years(39-77 years). Patient demographics and baseline characteristics were listed in Table 1. Stage FIGOII, III or IV, affected 2 (9.1%), 11 (50.0%) and 8 (36.4%) of patients, respectively. Most patients(86.4%)were high-grade serous cancer. All participants weighed less than 77 kg, 10 of who had basal platelet count less than 150,000 per cubic millimeter. The results of HRD testing were positive in six patients and negative in eight patients. Group assignment Patients who progresses during initial treatment, or completely alleviates after initial treatment (cytoreductive surgery and platinum-based chemotherapy), but recur within 6 months are defined as platinum-resistant ovarian cancer , who relapse more than 6 months are considered as platinum-sensitive ovarian cancer. According to the guidelines, patients are treated with three or more prior chemotherapy regimens and whose cancer is associated with HRD-positive defined by either: 1) a deleterious or suspected deleterious BRCA mutation; or 2) genomic instability and progression more than 6 months after response to the last platinum-based chemotherapy. And on this basis, the patients were divided into first-line maintenance treatment group and exploratory treatment group means who did not applied in the scope of indications, with six and sixteen patients in each group. There were three subgroups including exploratory second-line maintenance, front-line (less than three chemotherapy regimens) and multi-line (three or more prior chemotherapy regimens) treatment group, with one, six and nine patients in each group, respectively. Efficacy and HRD status In the first-line maintenance treatment group, all six patients are still on medication, two of whom are HRD-positive and four of whom are HRD unknown. In the exploratory treatment group, one patient (HRD-negative) diagnosed with highly differentiated papillary mesothelioma is on the second-line maintenance treatment. Serum CA125 of these patients with maintenance treatment were shown in Figure1. According to the different therapeutic strategy in the exploratory first-line therapy, three patients who did not undergo surgery and only receive chemotherapy for their personal willingness achieved SD after treated with niraparib. All three patients are still assessed as SD. Two patients with first platinum-sensitive recurrence ovarian cancer achieved SD, one of which was treated with niraparib monotherapy and the other one was treated with niraparib and anlotinib. One patient who did not receive chemotherapy after the surgery due to poor renal function achieved PD. The median prior line was 5 (3-8) in the exploratory multi-line therapy group. Ultimately therapeutic evaluation showed that two patients achieved partial response (PR), one patient achieved stable disease (SD) and three patients had progressive disease (PD), yielding the objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and the disease control rate (DCR) of 50% (95%CI=0.140-0.861) in patients with exploratory multi-line monotherapy. Also there were three patients treated with exploratory multi-line combined therapy, one patient achieved SD using niraparib combined with topotecan and anlotinib but another patient failed with this combination therapy. The remaining patient achieved PD by niraparib combined with anlotinib (Table 2). The status of HRD and tumor shrinkage in the exploratory front-line and multi-line treatment groups were listed in Figure2. Safety The most common AEs were nausea (54.5%), thrombocytopenia (40.9%), anemia (40.9%), fatigue or asthenia(36.4%) and decreased appetite(31.8%). Serious AEs (SAEs) (grade 3-4) were thrombocytopenia (18.2%), anemia (9.1%), neutropenia (9.1%), vomiting (4.5%) and dyspepsia (4.5%). Three patients with thrombocytopenia, neutropenia, or vomiting relieved through dose interruption and followed by dose reduction (200mg to 100mg). One patient given the combination therapy including niraparib, topotecan and anlotinib suffered Grade 4 thrombocytopenia within one week. She stopped taking the medicine and were treated with niraparib (200mg) monotherapy after treatment of elevated platelet count. One patient with dyspepsia could not stand drug-related AE after dose reduction and discontinued the treatment. Serious AEs were not found in two patients with initial dose of 100mg. We observed Leg swelling as a new adverse event in one patient. Summary of AEs were listed in Table 3. Discussion PARP inhibitor is a major advance in the treatment of ovarian cancer. Patients with BRCAmt or HRD-positive can get more profit from it. Now there are two kinds of PARP inhibitors including olaparib and niraparib in China. We previously reported the first real word study of olaparib in Chinese population[15].Here we presented the real word experience of niraparib in Chinese ovarian cancer patients. A retrospective analysis of ENGOT-OV16/NOVA trial suggested that patients with baseline body weight of<77 kg or baseline platelets of<150 000/ml might benefit from a starting dose of 200 mg/day following the NOVA trial [16]. A subsequent study proved that incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200mg/day in real-world practice versus patients initiating niraparib 300mg/day in ENGOT-OV16/NOVA in Caucasian population[17]. Recently the NORA trail demonstrated that niraparib maintenance therapy administered with an individual starting dose regimen, most subjects received the initial dose of 200mg/day, significantly improved the outcome in patients with recurrent ovarian cancer in 2020 ESMO meeting[11]. All subjects in our real world experience received 200mg/day according to the basal weight that was consistent with the results of prospective studies in Chinese population. At the 2020 ASCO meeting, an open-label, non-randomized study (LIGHT) showed that patients with platinum-sensitive recurrence, high-grade serous/endometrioid epithelial ovarian cancer and greater than or equal one prior line of platinum chemotherapy could benefit from olaparib monotherapy, especially in patients with HRD-positive[18]. Also in our exploratory front-line therapy group, two patients with first platinum-sensitive recurrence ovarian cancer achieved SD, one of which was with HRD-positive and the other was with HRD-negative. This finding needs to be confirmed by a prospective study of niraparib as front-line monotherapy. The PAOLA1 trail suggested that advanced ovarian cancer patients receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without BRCA mutation [19]. Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone in platinum-sensitive recurrent ovarian cancer[20]. One patient with HRD-negative also achieved SD using niraparib and anlotinib which might be related to the synergistic antitumor effects of PARP inhibitors and antiangiogenic drugs. It is also needed further studies to observe efficacy of the combination treatment in patient with HRD-negative, regardless of as front-line therapy and multi-line therapy. A multi-center, open-label, single-arm, phase 2 QUADRA trial observed that 10 (27%) of 37 platinum-resistance patients harbored BRCAmt, 12 (10%) of 120 platinum-resistance patients with HRD-positive and 5 (3%) of 169 platinum-resistance patients with HRD-negative in the primary efficacy population achieved an overall response according to RECIST1.1[12]. Regardless of the patients’ status of BRCA or HRD, Our results showed that the ORR of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in platinum-resistance ovarian cancer patients with exploratory multi-line monotherapy. We consider the differences of response to niraparib may be due to the small number of patients enrolled in our study and the criteria for enrollment in our real-world data. Previous studies confirmed that ovarian cancer patients with HRD-positive were more likely to benefit from niraparib than those with HRD-negative. We did not observe the relationship between efficacy and HRD status, which may be correlated with our small sample size. Approximately 50% of patients with high-grade serous ovarian cancer are HRD positive[21]. Twenty-one participants in our study harbored BRCAwt, 14 of who were tested with HRD panel. Of the 12 patients with high-grade serous ovarian cancer, 6 patients were with HRD- positive and 6 patients were with HRD-negative. The results were correspond to the study on large sample. The most common AEs were nausea, thrombocytopenia, anemia and fatigue. SAEs were thrombocytopenia, anemia, neutropenia and dyspepsia. The incidence of AEs and SAEs in our observation were similar to other studies. All SAEs occurred within one month after taking the medicine, most of which occurred within one week. Severe myelosuppression including thrombocytopenia and neutropenia, and vomiting were alleviated by dose reduction and interruption. Only patient with dyspepsia could not stand after dose reduction to 100mg/day and discontinued the treatment. The GOLD study did not meet its primary objective of showing a significant improvement in overall survival with olaparib in combination with a chemotherapeutic agent and in the overall or ATM-negative population of Asian patients with advanced gastric cancer due to the intolerable AEs[22]. In our study, one patient was given the combination therapy including niraparib, topotecan and anlotinib. She suffered Grade 4 thrombocytopenia within one week. Similar to the GOLD study, we also observed the intolerable AEs in patients using PARP inhibitors combined with chemotherapy. Conclusion This is the first real word data about niraparib in ovarian cancer patients with HRD status from China. Our findings demonstrated that Chinese population with niraparib 200mg orally once daily is feasible. Leg swelling was observed as a new adverse event in our study. HRD tests in our small samples confirmed that 50% of patients with high-grade serous ovarian cancer were HRD-positive. However, our data are limited representative due to the lower number of cases. It is needed further clinical trails to verify the exploratory therapy in our study. Abbreviations PARP: poly (ADP-ribose) polymerase HRD: homologous recombination deficiency HRR: homologous recombination repair PFI: Platinum-free-interval RECIST: Response Evaluation Criteria in Solid Tumors; Declarations Ethics approval and consent to participate This study was approved by the institutional review board of Jiangsu Cancer Hospital, Nanjing Medical University, China. The informed consent requirement was waived. The committee’s reference number was Jiangsu Cancer Hospital’s Ethical Committee 2020-068. Consent for publication Not applicable. Availability of Data and Materials We would not share the data and material used in this manuscript, because we need them for further research. Competing interests The authors declare that they have no competing interests. Funding This study was supported by grants from the National Natural Science Foundation of China (No. 81472441, 81501205) , Institute level project of Jiangsu Cancer Hospital(No. ZM201804) and Beijing Kanghua Foundation for the Development of Traditional Chinese and Western Medicine -Le Fund (KH-2020-LJJ-021). Authors’ contributions Jing Ni participated in the design of present study and drafted the manuscript. Xianzhong Cheng carried out the cases recruit of present study. Qian Zhao and Hongyuan Gu participated in the cases recruit of present study. Wenwen Guo and Rui Zhou carried out statistical analysis. Zhiqin Dai and Xia Xu participated in the statistical analysis and drafted the manuscript. Xiaoxiang Chen designed of the study, performed the statistical analysis and revised the manuscript. All authors read and approved the final manuscript. Acknowledgments Not applicable. Authors’ information Jing Ni, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] ; Xianzhong Cheng, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] ; Qian Zhao, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] ; Zhiqin Dai, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] ; Xia Xu, Department of Chemotherapy, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] ; Wenwen Guo, Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, PR China, [email protected] ; Hongyuan Gu, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] ; Rui Zhou, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected] . *Correspondence author: Xiaoxiang Chen, M.D., Ph.D., Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42# Baiziting street, Nanjing, Jiangsu, 210009, People's Republic of China; Fax and telephone: +86-25-83284675; E-mail: [email protected] References Coleridge SL, et al. 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Schiewer MJ, et al. PARP-1 regulates DNA repair factor availability. EMBO Mol Med. 2018;10(12): e8816. Heo YA, Duggan ST. Niraparib: A Review in Ovarian Cancer. Target Oncol. 2018;13(4): 533-9. Ison G, et al. FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy. Clin Cancer Res. 2018; 24(17): 4066-71. Wu XH, et al. Individualized Starting Dose of Niraparib in Patients with Platinum-Sensitive Recurrent Ovarian Cancer (NORA) : A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial. 2020. Proc Euro Soc Med Oncol. Moore KN, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):636-48. Richards S, et al. 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Olaparib treatment in patients (pts) with platinum-sensitive relapsed (PSR) ovarian cancer (OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Phase II LIGHT study. 2020. Proc Am Soc Clin Oncol. Ray-Coquard I, et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381(25): 2416-28. Mirza MR, et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019;20(10):1409-19. Iijima M, et al. Genome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer. Oncol Lett. 2017;13(3):1063-70. Bang YJ, et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12): 1637-51. Tables Table 1 Baseline characteristics in 22 patients. Values are reported as frequency (n [%]) or as mean (range). Characteristic Number of patients (percent) Age, yrs Median age (range) 55 (39-77) ≤55 12 (54.5) >55 10 (45.5) Primary tumor location Ovary 21 (95.5) Fallopian tube 1 (4.5) International FIGO stage Ⅱ 2 (9.1) Ⅲ 11 (50.0) Ⅳ 8 (36.4) Unknown 1 (4.5) Histological type High-grade serous 19 (86.4) Low-grade serous 1 (4.5) Other 1 (4.5) Unknown 1 (4.5) Family history of cancer Yes 9 (40.9) No 13 (59.1) ECOG 0 8 (36.4) 1 13 (59.1) 2 1 (4.5) Baseline body weight ≥77 kg 0 (0) <77 kg 22 (100) Platelet count ≥150×10 9 /L 12 (54.5) <150×10 9 /L 10 (45.5) HRD status HRD-positive 6 (27.3) tBRCA-mutated 1 (4.5) BRCA-wild type or BRCA-unknown and HRD-positive 5 (22.7) HRD-negative 8 (36.4) HRD unknown 8 (36.4) Prior lines of chemotherapy ≤1 12 (54.5) >1 10 (45.5) Platinum status Platinum-sensitive 5 (22.7) Platinum-resistant 5 (22.7) Unknown 12 (54.5) Categories of therapy First-line maintenance therapy 6 (27.3) Exploratory therapy 16 (72.7) Exploratory second-line maintenance therapy 1 (4.5) Exploratory Front-line therapy 6 (27.3) Exploratory multi-line therapy 9 (40.9) NACT+IDS Yes 7 (31.8) No 15 (68.2) Primary debulking surgery Yes 12 (54.5) No 10 (45.5) Secondary cytoreductive surgery Yes 3 (13.6) No 19 (86.4) Combination with other agents Yes 4 (18.2) No 18 (81.8) Abbreviations: FIGO, International Federation of Gynecology and Obstetrics; ECOG, Eastern Cooperative Oncology Group; HRD, homologous recombination deficiency; NACT, Neoadjuvant chemotherapy; IDS, Interval debulking surgery. Table 2 Short-term efficacy of 9 evaluable patients with exploratory multi-line therapy. Short-term efficacy Monotherapy, n (%) Combined Treatment, n (%) Complete response (CR) 0 (0) 0 (0) Partial response (PR) 2 (33.3) 0 (0) Stable disease (SD) 1 (16.7) 1 (33.3) Progression disease (PD) 3 (50.0) 2 (66.7) Objective response rate (ORR) 2 (33.3) 0 (0) Disease control rate (DCR) 3 (50.0) 1 (33.3) The table above showed the short-term efficacy of 9 evaluable patients with exploratory multi-line therapy including 6 patients with niraparib monotherapy and 3 patients with combined treatment. Short-term efficacy was classified by modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Table 3 Summary of Adverse Events Adverse Event Any Grade Grade 3 or 4 Number of patients (percent) Nausea 12 (54.5) 0 (0) Thrombocytopenia 11 (50.0) 4 (18.2) Anemia 9 (40.9) 2 (9.1) Fatigue or asthenia 8 (36.4) 0 (0) Decreased appetite 7 (31.8) 0 (0) Constipation 6 (27.3) 0 (0) Neutropenia 5 (22.7) 2 (9.1) Insomnia 5 (22.7) 0 (0) Vomiting 3 (13.6) 1 (4.5) Dyspepsia 3 (13.6) 1 (4.5) Headache 3 (13.6) 0 (0) Dizziness 2 (9.1) 0 (0) Abdominal distention 2 (9.1) 0 (0) Abdominal pain 1 (4.5) 0 (0) Dysgeusia 1 (4.5) 0 (0) Back pain 1 (4.5) 0 (0) Diarrhea 1 (4.5) 0 (0) Maculopapular rash 1 (4.5) 0 (0) Stomatitis 1 (4.5) 0 (0) Dry mouth 1 (4.5) 0 (0) Newly observed Leg swelling 1 (4.5) 0 (0) Led to discontinuation of intervention 1 (4.5) - Led to dose reduction 4 (18.2) - Led to dose interruption 4 (18.2) - Note: Adverse events were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Cite Share Download PDF Status: Published Journal Publication published 17 May, 2021 Read the published version in Journal of Ovarian Research → Version 1 posted Review # 2 received at journal 06 Feb, 2021 Editorial decision: Minor revision 06 Feb, 2021 Review # 1 received at journal 01 Feb, 2021 Reviewer # 3 agreed at journal 30 Jan, 2021 Reviewer # 2 agreed at journal 27 Jan, 2021 Reviewer # 1 agreed at journal 26 Jan, 2021 Reviewers invited by journal 07 Nov, 2020 Editor assigned by journal 02 Nov, 2020 Editor invited by journal 02 Nov, 2020 Submission checks completed at journal 02 Nov, 2020 First submitted to journal 30 Oct, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-101839","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":4325425,"identity":"2ad4b5e9-4aa9-4d08-8d31-40b0ea9ce952","order_by":0,"name":"Jing Ni","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Ni","suffix":""},{"id":4325426,"identity":"32c6293f-3e1b-4660-9bdc-b7c3db139d53","order_by":1,"name":"Xianzhong Cheng","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xianzhong","middleName":"","lastName":"Cheng","suffix":""},{"id":4325427,"identity":"195caadf-7fe5-4fe4-818a-a6f8eb344fe8","order_by":2,"name":"Qian Zhao","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Zhao","suffix":""},{"id":4325428,"identity":"bd4fbf10-67b1-45a1-af13-188c2c84554c","order_by":3,"name":"Zhiqin Dai","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhiqin","middleName":"","lastName":"Dai","suffix":""},{"id":4325429,"identity":"3d9f3e2a-ad95-441d-959c-d6ceaa038e91","order_by":4,"name":"Xia Xu","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xia","middleName":"","lastName":"Xu","suffix":""},{"id":4325430,"identity":"f428a2a7-2610-450a-ad3d-7b845d97077e","order_by":5,"name":"Wenwen Guo","email":"","orcid":"","institution":"The Second Affliated Hospotal of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenwen","middleName":"","lastName":"Guo","suffix":""},{"id":4325431,"identity":"e9fb9221-173f-47cd-84b6-20d2c7676e7b","order_by":6,"name":"Hongyuan Gu","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongyuan","middleName":"","lastName":"Gu","suffix":""},{"id":4325432,"identity":"f89f26da-6ccc-445f-8a94-69720f3211fc","order_by":7,"name":"Rui Zhou","email":"","orcid":"","institution":"Jiangsu Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Zhou","suffix":""},{"id":4325433,"identity":"7392e40d-c7d6-451f-88c3-4be6eb2a5a97","order_by":8,"name":"xiaoxiang chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYBADxn4QmVBAipaZDSAtBqRo2XAARBGjhX9Gjpk0T81h2c3nVyd+eGDAIM8vdgC/Fokzx5INZxw7bLztxtvNEkCHGc6cnYBfiwF788EHHxsOJ267cXYDSEuCwW1CWpgZGw4kArVsnnF28w/itMBs2cDfu404W6B+STeecYN3m0WCgQRhv0BDzFq2v//s5ps/Kmzk+aUJaIGCZqB9YJUSRCkHgTqgfQeIVj0KRsEoGAUjDAAAePBIHwPnanAAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-2400-4749","institution":"Jiangsu Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"xiaoxiang","middleName":"","lastName":"chen","suffix":""}],"badges":[],"createdAt":"2020-11-02 13:31:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-101839/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-101839/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13048-021-00803-2","type":"published","date":"2021-05-17T20:57:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":3426896,"identity":"86893e69-578d-47f4-9abe-0d05281d00d0","added_by":"auto","created_at":"2020-11-06 14:53:55","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":68433,"visible":true,"origin":"","legend":"Serum CA125 values in each group.\nNote: The CA125 level of the first follow-up was used as the reference value, and all data were converted to natural logarithm. CA125 follow-up data were obtained from 6 patient in the first-line maintenance treatment group and 16 patients in the exploratory therapy group.\n","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-101839/v1/4f596913fb5c37b1348dd70d.jpg"},{"id":3426897,"identity":"dfcccb26-99f0-4fb9-93f3-b593b3fc1735","added_by":"auto","created_at":"2020-11-06 14:53:55","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":70931,"visible":true,"origin":"","legend":"Waterfall plot of 13 evaluable patients with exploratory therapy.\nNote: Tumor burden change per investigator review. Maximum reduction from baseline (or smallest increase from baseline for patients with no reductions) in the sum of the longest diameters of target lesions. The change from baseline in tumor measurement as assessed by investigator review is shown for 13 evaluable patients (per protocol set). Front-line exploratory subgroup and multi-line exploratory subgroup were shown with different color in the figure. Among them, there were 3 HRD-positive patients, 6 HRD-negative patients and 4 HRD-unknown patients. Ten of them were treated by niraparib monotherapy while 3 of them(patient 1,7,11) were treated by combined strategies. The dotted line represents the threshold for partial response (\u003e30% reduction from baseline sum of longest diameters) and progressive disease (\u003e20% increase from baseline sum of longest diameters). Target lesions were defined according to RECIST 1.1.\n","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-101839/v1/eba7b71dcebd9d4354f9045d.jpg"},{"id":13612137,"identity":"f1f609a9-33c6-414d-bb6a-7ea832f41590","added_by":"auto","created_at":"2021-09-17 06:31:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":422080,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-101839/v1/d1268a77-ee1f-45fe-9621-1e5f31258f6c.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eOvarian cancer is the most lethal gynecological malignancy, 70% of the patients are diagnosed with advanced stage. Although most ovarian cancer patients are sensitive to standard first-line treatment including cytoreductive surgery and platinum-based chemotherapy, about 80% patients relapse within 1 to 2 years after initial treatment and gradually progress to platinum-resistance ovarian cancer, accompanied by significantly shortened survival[1,2]. How to prolong the platinum free interval (PFI) becomes one of the breakthrough points in ovarian cancer treatment. Recently, poly ADP-ribose Polymerase (PARP) inhibitors have changed the treatment paradigm for ovarian cancer that can significantly improve the platinum free interval, and finally prolong the overall survival of patients with BRCA mutation [3-6].\u003c/p\u003e\n\u003cp\u003ePARP is a specific DNA fracture receptor, which is activated after DNA damage, recognizes and binds to the DNA fracture site, and mediates DNA single-strand damage repair in tumor cells[7]. PARP inhibitor can lead to DNA double strand damage inducing by amount of DNA single-strand damage. In homologous recombination deficiency (HRD) tumor cells, such as BRCA mutation or other germline mutations in homologous recombination repair (HRR) pathway genes (e.g., RAD51 and ATM), can not repair DNA single-strand damage, forming the synthetic lethal effect[8]. Therefore, BRCAmt or HRD positive tumor cells are more sensitive to PARP inhibitors in terms of molecular mechanisms.\u003c/p\u003e\n\u003cp\u003eNiraparib (Zejula\u003csup\u003e\u0026reg;\u003c/sup\u003e), is a highly selective inhibitor of PARP1/2, nuclear proteins that detect DNA damage and promote its repair[9]. In 2017, it was firstly approved for second-line maintenance treatment of ovarian cancer patients who were in complete or partial response to platinum-based chemotherapy by Food and Drug Administration (FDA) according to the study of NOVA[3,10]. Another study observed the significant efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after response to first-line platinum-based chemotherapy[5]. Both of the NOVA and PRIMA studies found that patients with HRD positive can get more profit from niraparib. Recently the first fully powered, multi-center, phase III clinical study in Chinese population (NORA) showed that median PFS was significantly longer for niraparib as second-line maintenance treatment versus placebo among patients with germline BRCA mutations (not reached vs. 5.5 months; HR was 0.22) and those without germline BRCA mutations (11.1 vs. 3.9 months; HR was 0.40) in 2020 ESMO meeting[11]. QUADRA study demonstrated that niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which included not only patients with BRCA mutation but also population with BRCA wild-type [12].\u003c/p\u003e\n\u003cp\u003eHowever, there was no real-world data to illustrate the efficacy and safety of niraparib in Chinese population. We conducted this study to assess the real-world clinical impact of niraparib in ovarian cancer patients with HRD status.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with advanced ovarian cancer who received niraparib from June 2019 to July 2020 were included in Jiangsu Cancer Hospital. We collected the basic characteristics of these patients, including age, Eastern Cooperative Oncology Group performance status (ECOG PS) before the start of the treatment, histological type, clinical stage on the basis of Federation International of Gynecology and Obstetrics (FIGO), basal body weight, basal platelet count, previous therapy before and after the treatment of niraparib and the follow-up. The study was approved by the ethics committee of Jiangsu Cancer Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDosing Regimen\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe initial dose was base on the level of basal body weight or platelet count. Patients with basal body weight \u0026ge;77kg and basal platelet count of \u0026ge;150,000/microliter (\u0026mu;L) will take 300 mg daily. While patients with basal body weight\u0026lt;77 kg and/or basal platelet count\u0026lt;150,000/\u0026mu;Lwill take 200 mg daily. Dose reduction (300mg to 200mg or 100mg; 200mg to 100mg) or interruption for drug-related AEs was allowed. Serum CA125 and imaging examinations were performed on each patient at baseline, followed by a monthly examination of CA125 and imaging examinations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHRD testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe paraffin sections from the cytoreductive surgery were obtained after patients\u0026rsquo; informed consent. DNA was extracted from FFPE biopsy/surgical specimens; 50 to 200 ng DNA undergoes library construction and hybrid capture with AmoyDx\u003csup\u003e\u0026reg;\u003c/sup\u003e HRD panel, which selected coding\u0026ensp;sequences\u0026ensp;(CDS) regions for 54 HRR pathway genes and 72000 single nucleotide polymorphisms (SNPs) for HRD calling. The selected libraries were pooled and sequenced on the Illumina Novaseq6000 to \u0026gt;500\u0026times; unique coverage for 54 HRR genes and \u0026gt;100\u0026times; for SNP loci.\u003c/p\u003e\n\u003cp\u003eSequence data was processed using a customized analysis pipeline designed to accurately detect multiple classes of genomic alterations: base substitutions, short insertions/deletions with detection sensitivity at variant allele frequency (VAF) \u0026ge;5%. Detected mutations were annotated according to American College of Medical Genetics (ACMG) guideline[13] and classified as pathogenic, likely pathogenic, variants of unknown significance, likely benign and benign. HRD score was calculated by the sum of three types of genomic instable events including loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transition (LST) defined by ref[14]. HRD-positive was defined by either BRCA1/2 pathogenic or likely pathogenic mutation or HRD score \u0026ge;42.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic and baseline data were summarized and analyzed. The efficacy was assessed as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) by RECIST 1.1. Objective response rate (ORR) was defined as the proportion of patients achieving CR or PR. Disease control rate (DCR) was defined as the proportion of patients achieving CR, PR or SD for at least 8 weeks. Treatment-related adverse events (AEs) were graded according to CTCAE 5.0.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 95% confidence interval was calculated using the Wilson procedure with a correction for continuity. Data were statistically analyzed using SPSS version 19.0 professional statistical software and all the count data were expressed as a percentage (%).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatients\u0026rsquo; characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of twenty-two patients treated with niraparib were enrolled, of whom twenty-one patients were ovary cancer and one patient was fallopian tube cancer. The median age was 55.0 years(39-77 years). Patient demographics and baseline characteristics were listed in Table 1. Stage FIGOII, III or IV, affected 2 (9.1%), 11 (50.0%) and 8 (36.4%) of patients, respectively. Most patients(86.4%)were high-grade serous cancer. All participants weighed less than 77 kg, 10 of who had basal platelet count less than 150,000 per cubic millimeter. The results of HRD testing were positive in six patients and negative in eight patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup assignment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients who progresses during initial treatment, or completely alleviates after initial treatment (cytoreductive surgery and platinum-based chemotherapy), but recur within 6 months are defined as platinum-resistant ovarian cancer , who relapse more than 6 months are considered as platinum-sensitive ovarian cancer. According to the guidelines, patients are treated with three or more prior chemotherapy regimens and whose cancer is associated with HRD-positive defined by either: 1) a deleterious or suspected deleterious BRCA mutation; or 2) genomic instability and progression more than 6 months after response to the last platinum-based chemotherapy. And on this basis, the patients were divided into first-line maintenance treatment group and exploratory treatment group means who did not applied in the scope of indications, with six and sixteen patients in each group. There were three subgroups including exploratory second-line maintenance, front-line (less than three chemotherapy regimens) and multi-line (three or more prior chemotherapy regimens) treatment group, with one, six and nine patients in each group, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEfficacy and HRD status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the first-line maintenance treatment group, all six patients are still on medication, two of whom are HRD-positive and four of whom are HRD unknown. In the exploratory treatment group, one patient (HRD-negative) diagnosed with highly differentiated papillary mesothelioma is on the second-line maintenance treatment. Serum CA125 of these patients with maintenance treatment were shown in Figure1.\u003c/p\u003e\n\u003cp\u003eAccording to the different therapeutic strategy in the exploratory first-line therapy, three patients who did not undergo surgery and only receive chemotherapy for their personal willingness achieved SD after treated with niraparib. All three patients are still assessed as SD. Two patients with first platinum-sensitive recurrence ovarian cancer achieved SD, one of which was treated with niraparib monotherapy and the other one was treated with niraparib and anlotinib. One patient who did not receive chemotherapy after the surgery due to poor renal function achieved PD.\u003c/p\u003e\n\u003cp\u003eThe median prior line was 5 (3-8) in the exploratory multi-line therapy group. Ultimately therapeutic evaluation showed that two patients achieved partial response (PR), one patient achieved stable disease (SD) and three patients had progressive disease (PD), yielding the objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and the disease control rate (DCR) of 50% (95%CI=0.140-0.861) in patients with exploratory multi-line monotherapy. Also there were three patients treated with exploratory multi-line combined therapy, one patient achieved SD using niraparib combined with topotecan and anlotinib but another patient failed with this combination therapy. The remaining patient achieved PD by niraparib combined with anlotinib (Table 2). The status of HRD and tumor shrinkage in the exploratory front-line and multi-line treatment groups were listed in Figure2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe most common AEs were nausea (54.5%), thrombocytopenia (40.9%), anemia (40.9%), fatigue or asthenia(36.4%) and decreased appetite(31.8%). Serious AEs (SAEs) (grade 3-4) were thrombocytopenia (18.2%), anemia (9.1%), neutropenia (9.1%), vomiting (4.5%) and dyspepsia (4.5%). Three patients with thrombocytopenia, neutropenia, or vomiting relieved through dose interruption and followed by dose reduction (200mg to 100mg). One patient given the combination therapy including niraparib, topotecan and anlotinib suffered Grade 4 thrombocytopenia within one week. She stopped taking the medicine and were treated with niraparib (200mg) monotherapy after treatment of elevated platelet count. One patient with dyspepsia could not stand drug-related AE after dose reduction and discontinued the treatment. Serious AEs were not found in two patients with initial dose of 100mg. We observed Leg swelling as a new adverse event in one patient. Summary of AEs were listed in Table 3.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePARP inhibitor is a major advance in the treatment of ovarian cancer. Patients with BRCAmt or HRD-positive can get more profit from it. Now there are two kinds of PARP inhibitors including olaparib and niraparib in China. We previously reported the first real word study of olaparib in Chinese population[15].Here we presented the real word experience of niraparib in Chinese ovarian cancer patients.\u003c/p\u003e\n\u003cp\u003eA retrospective analysis of ENGOT-OV16/NOVA trial suggested that patients with baseline body weight of\u0026lt;77 kg or baseline platelets of\u0026lt;150 000/ml might benefit from a starting dose of 200 mg/day following the NOVA trial [16]. A subsequent study proved that incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200mg/day in real-world practice versus patients initiating niraparib 300mg/day in ENGOT-OV16/NOVA in Caucasian population[17]. Recently the NORA trail demonstrated that niraparib maintenance therapy administered with an individual starting dose regimen, most subjects received the initial dose of 200mg/day, significantly improved the outcome in patients with recurrent ovarian cancer in 2020 ESMO meeting[11]. All subjects in our real world experience received 200mg/day according to the basal weight that was consistent with the results of prospective studies in Chinese population.\u003c/p\u003e\n\u003cp\u003eAt the 2020 ASCO meeting, an open-label, non-randomized study (LIGHT) showed that patients with platinum-sensitive recurrence, high-grade serous/endometrioid epithelial ovarian cancer and greater than or equal one prior line of platinum chemotherapy could benefit from olaparib monotherapy, especially in patients with HRD-positive[18]. Also in our exploratory front-line therapy group, two patients with first platinum-sensitive recurrence ovarian cancer achieved SD, one of which was with HRD-positive and the other was with HRD-negative. This finding needs to be confirmed by a prospective study of niraparib as front-line monotherapy.\u003c/p\u003e\n\u003cp\u003eThe PAOLA1 trail suggested that advanced ovarian cancer patients receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without BRCA mutation\u003c/p\u003e\n\u003cp\u003e[19]. Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone in platinum-sensitive recurrent ovarian cancer[20]. One patient with HRD-negative also achieved SD using niraparib and anlotinib which might be related to the synergistic antitumor effects of PARP inhibitors and antiangiogenic drugs. It is also needed further studies to observe efficacy of the combination treatment in patient with HRD-negative, regardless of as front-line therapy and multi-line therapy.\u003c/p\u003e\n\u003cp\u003eA multi-center, open-label, single-arm, phase 2 QUADRA trial observed that 10 (27%) of 37 platinum-resistance patients harbored BRCAmt, 12 (10%) of 120 platinum-resistance patients with HRD-positive and 5 (3%) of 169 platinum-resistance patients with HRD-negative in the primary efficacy population achieved an overall response according to RECIST1.1[12]. Regardless of the patients\u0026rsquo; status of BRCA or HRD, Our results showed that the ORR of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in platinum-resistance ovarian cancer patients with exploratory multi-line monotherapy. We consider the differences of response to niraparib may be due to the small number of patients enrolled in our study and the criteria for enrollment in our real-world data.\u003c/p\u003e\n\u003cp\u003ePrevious studies confirmed that ovarian cancer patients with HRD-positive were more likely to benefit from niraparib than those with HRD-negative. We did not observe the relationship between efficacy and HRD status, which may be correlated with our small sample size. Approximately 50% of patients with high-grade serous ovarian cancer are HRD positive[21]. Twenty-one participants in our study harbored BRCAwt, 14 of who were tested with HRD panel. Of the 12 patients with high-grade serous ovarian cancer, 6 patients were with HRD- positive and 6 patients were with HRD-negative. The results were correspond to the study on large sample.\u003c/p\u003e\n\u003cp\u003eThe most common AEs were nausea, thrombocytopenia, anemia and fatigue. SAEs were thrombocytopenia, anemia, neutropenia and dyspepsia. The incidence of AEs and SAEs in our observation were similar to other studies. All SAEs occurred within one month after taking the medicine, most of which occurred within one week.\u003c/p\u003e\n\u003cp\u003eSevere myelosuppression including thrombocytopenia and neutropenia, and vomiting were alleviated by dose reduction and interruption. Only patient with dyspepsia could not stand after dose reduction to 100mg/day and discontinued the treatment. The GOLD study did not meet its primary objective of showing a significant improvement in overall survival with olaparib in combination with a chemotherapeutic agent and in the overall or ATM-negative population of Asian patients with advanced gastric cancer due to the intolerable AEs[22]. In our study, one patient was given the combination therapy including niraparib, topotecan and anlotinib. She suffered Grade 4 thrombocytopenia within one week. Similar to the GOLD study, we also observed the intolerable AEs in patients using PARP inhibitors combined with chemotherapy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis is the first real word data about niraparib in ovarian cancer patients with HRD status from China. Our findings demonstrated that Chinese population with niraparib 200mg orally once daily is feasible. Leg swelling was observed as a new adverse event in our study. HRD tests in our small samples confirmed that 50% of patients with high-grade serous ovarian cancer were HRD-positive. However, our data are limited representative due to the lower number of cases. It is needed further clinical trails to verify the exploratory therapy in our study.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePARP: poly (ADP-ribose) polymerase\u003c/p\u003e\n\u003cp\u003eHRD: homologous recombination deficiency\u003c/p\u003e\n\u003cp\u003eHRR: homologous recombination repair\u003c/p\u003e\n\u003cp\u003ePFI: Platinum-free-interval\u003c/p\u003e\n\u003cp\u003eRECIST: Response Evaluation Criteria in Solid Tumors;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional review board of Jiangsu Cancer Hospital, Nanjing Medical University, China. The informed consent requirement was waived. The committee\u0026rsquo;s reference number was Jiangsu Cancer Hospital\u0026rsquo;s Ethical Committee 2020-068.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would not share the data and material used in this manuscript, because we need\u003c/p\u003e\n\u003cp\u003ethem for further research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from the National Natural Science Foundation of China (No. 81472441, 81501205) , Institute level project of Jiangsu Cancer Hospital(No. ZM201804) and Beijing Kanghua Foundation for the Development of Traditional Chinese and Western Medicine -Le Fund (KH-2020-LJJ-021).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJing Ni participated in the design of present study and drafted the manuscript. Xianzhong Cheng carried out the cases recruit of present study. Qian Zhao and Hongyuan Gu participated in the cases recruit of present study. Wenwen Guo and Rui Zhou carried out statistical analysis. Zhiqin Dai and Xia Xu participated in the statistical analysis and drafted the manuscript. Xiaoxiang Chen designed of the study, performed the statistical analysis and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJing Ni, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected]; Xianzhong Cheng, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected]; Qian Zhao, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China,[email protected]; Zhiqin Dai, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected]; Xia Xu, Department of Chemotherapy, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected]; Wenwen Guo, Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, PR China, [email protected]; Hongyuan Gu, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, [email protected]; Rui Zhou, Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, PR China, \u003ca href=\"mailto:[email protected]\"\[email protected]\u003c/a\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*Correspondence author: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXiaoxiang Chen, M.D., Ph.D., Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42# Baiziting street, Nanjing, Jiangsu, 210009, People's Republic of China;\u003c/p\u003e\n\u003cp\u003eFax and telephone: +86-25-83284675;\u003c/p\u003e\n\u003cp\u003eE-mail: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eColeridge SL, et al. Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev. 2019;10:CD005343.\u003c/li\u003e\n\u003cli\u003eGuan LY, Lu Y. New developments in molecular targeted therapy of ovarian cancer. Discov Med. 2018;26(144):219-29.\u003c/li\u003e\n\u003cli\u003eMirza MR, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016;375(22):2154-64.\u003c/li\u003e\n\u003cli\u003eLedermann J, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382-92.\u003c/li\u003e\n\u003cli\u003eGonz\u0026aacute;lez-Mart\u0026iacute;n A, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019;381(25): 2391-402.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"6\"\u003e\n\u003cli\u003ePoveda A, et al. Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. 2020. Proc Am Soc Clin Oncol.\u003c/li\u003e\n\u003cli\u003eMurai J, et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012;72(21): 5588-99.\u003c/li\u003e\n\u003cli\u003eSchiewer MJ, et al. PARP-1 regulates DNA repair factor availability. EMBO Mol Med. 2018;10(12): e8816.\u003c/li\u003e\n\u003cli\u003eHeo YA, Duggan ST. Niraparib: A Review in Ovarian Cancer. Target Oncol. 2018;13(4): 533-9.\u003c/li\u003e\n\u003cli\u003eIson G, et al. FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy. Clin Cancer Res. 2018; 24(17): 4066-71.\u003c/li\u003e\n\u003cli\u003eWu XH, et al. Individualized Starting Dose of Niraparib in Patients with Platinum-Sensitive Recurrent Ovarian Cancer (NORA) : A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial. 2020. Proc Euro Soc Med Oncol.\u003c/li\u003e\n\u003cli\u003eMoore KN, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):636-48.\u003c/li\u003e\n\u003cli\u003eRichards S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5): 405-24.\u003c/li\u003e\n\u003cli\u003eTimms KM, et al. Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res. 2014;16(6): 475.\u003c/li\u003e\n\u003cli\u003eNi J, et al. Olaparib in the therapy of advanced ovarian cancer: first real world experiences in safety and efficacy from China. J Ovarian Res. 2019;12(1): 117.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"16\"\u003e\n\u003cli\u003eBerek JS, et al. Safety and dose modification for patients receiving niraparib. Ann Oncol. 2018; 29(8):1784-92.\u003c/li\u003e\n\u003cli\u003eGallagher JR, et al. Real-world adverse events with niraparib 200 mg/day maintenance therapy in ovarian cancer: a retrospective study. Future Oncol. 2019;15(36): 4197-206.\u003c/li\u003e\n\u003cli\u003eCadoo K, et al. Olaparib treatment in patients (pts) with platinum-sensitive relapsed (PSR) ovarian cancer (OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Phase II LIGHT study. 2020. Proc Am Soc Clin Oncol.\u003c/li\u003e\n\u003cli\u003eRay-Coquard I, et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381(25): 2416-28.\u003c/li\u003e\n\u003cli\u003eMirza MR, et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019;20(10):1409-19.\u003c/li\u003e\n\u003cli\u003eIijima M, et al. Genome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer. Oncol Lett. 2017;13(3):1063-70.\u003c/li\u003e\n\u003cli\u003eBang YJ, et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12): 1637-51.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Baseline characteristics in 22 patients. Values are reported as frequency (n [%]) or as mean (range).\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eCharacteristic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eNumber of patients (percent)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eAge, yrs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eMedian age (range)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e55 (39-77)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026le;55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e12 (54.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026gt;55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e10 (45.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePrimary tumor location\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eOvary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e21 (95.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eFallopian tube\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eInternational FIGO stage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eⅡ\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eⅢ\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e11 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eⅣ\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e8 (36.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eUnknown\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eHistological type\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eHigh-grade serous\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e19 (86.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eLow-grade serous\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eOther\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eUnknown\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eFamily history of cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e9 (40.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e13 (59.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eECOG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e8 (36.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e13 (59.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eBaseline body weight\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026ge;77 kg\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026lt;77 kg\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e22 (100)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePlatelet count\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026ge;150\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e12 (54.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026lt;150\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e10 (45.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eHRD status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eHRD-positive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e6 (27.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003etBRCA-mutated\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eBRCA-wild type or BRCA-unknown and HRD-positive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e5 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eHRD-negative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e8 (36.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eHRD unknown\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e8 (36.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePrior lines of chemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026le;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e12 (54.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003e\u0026gt;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e10 (45.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePlatinum status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePlatinum-sensitive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e5 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePlatinum-resistant\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e5 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eUnknown\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e12 (54.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eCategories of therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eFirst-line maintenance therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e6 (27.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eExploratory therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e16 (72.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eExploratory second-line maintenance therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eExploratory Front-line therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e6 (27.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eExploratory multi-line therapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e9 (40.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eNACT+IDS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e7 (31.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e15 (68.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003ePrimary debulking surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e12 (54.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e10 (45.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eSecondary cytoreductive surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e3 (13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e19 (86.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eCombination with other agents\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e4 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"359\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e18 (81.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: FIGO, International Federation of Gynecology and Obstetrics; ECOG, Eastern Cooperative Oncology Group; HRD, homologous recombination deficiency; NACT, Neoadjuvant chemotherapy; IDS, Interval debulking surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u003c/strong\u003eShort-term efficacy of 9 evaluable patients with exploratory multi-line therapy.\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003eShort-term efficacy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003eMonotherapy, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eCombined Treatment, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003eComplete response (CR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003ePartial response (PR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e2 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003eStable disease (SD)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e1 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e1 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003eProgression disease (PD)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e3 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e2 (66.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003eObjective response rate (ORR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e2 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"197\"\u003e\n\u003cp\u003eDisease control rate (DCR)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"171\"\u003e\n\u003cp\u003e3 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e1 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe table above showed the short-term efficacy of 9 evaluable patients with exploratory multi-line therapy including 6 patients with niraparib monotherapy and 3 patients with combined treatment. Short-term efficacy was classified by modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 \u003c/strong\u003eSummary of Adverse Events\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"236\"\u003e\n\u003cp\u003eAdverse Event\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003eAny Grade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003eGrade 3 or 4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"317\"\u003e\n\u003cp\u003eNumber of patients (percent)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eNausea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e12 (54.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eThrombocytopenia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e11 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e4 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eAnemia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e9 (40.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eFatigue or asthenia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e8 (36.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eDecreased appetite\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e7 (31.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eConstipation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e6 (27.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eNeutropenia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e5 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eInsomnia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e5 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eVomiting\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e3 (13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eDyspepsia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e3 (13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eHeadache\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e3 (13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eDizziness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eAbdominal distention\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eAbdominal pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eDysgeusia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eBack pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eDiarrhea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eMaculopapular rash\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eStomatitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eDry mouth\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eNewly observed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eLeg swelling\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eLed to discontinuation of intervention\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e1 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eLed to dose reduction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e4 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"236\"\u003e\n\u003cp\u003eLed to dose interruption\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"138\"\u003e\n\u003cp\u003e4 (18.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"179\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Adverse events were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Advanced ovarian cancer, Niraparib, Real World, Efficacy, Safety, HRD","lastPublishedDoi":"10.21203/rs.3.rs-101839/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-101839/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\u003cp\u003eNiraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD) positive. We present real-world experience from China. \u003c/p\u003e\u003cp\u003eMethods\u003c/p\u003e\u003cp\u003ePatients with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx\u003csup\u003e®\u003c/sup\u003e) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. \u003c/p\u003e\u003cp\u003eResults\u003c/p\u003e\u003cp\u003eTwenty-two patients all received niraparib at an bolus of 200mg/d. 50% of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in the exploratory multi-line monotherapy group. Commonly AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. \u003c/p\u003e\u003cp\u003eConclusion\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ql-cursor\"\u003e\u003c/span\u003eIt is feasible for patients received a bolus of 200mg/d in Chinese population with promising efficacy and well tolerated. This is first real world data about niraparib in ovarian cancer patients with HRD status from China.\u003c/p\u003e","manuscriptTitle":"The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-11-06 14:53:53","doi":"10.21203/rs.3.rs-101839/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2021-02-07T00:00:00+00:00","index":2,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"decision","content":"Minor revision","date":"2021-02-07T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-02-02T00:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2021-01-31T00:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-01-28T00:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-01-27T00:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-11-08T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-11-03T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-11-02T23:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-11-02T13:31:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-10-31T00:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"326beb41-b5b6-4665-b892-1ce4e5e694b4","owner":[],"postedDate":"November 6th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":997101,"name":"Sexual \u0026 Reproductive Medicine"},{"id":997102,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2021-07-27T20:57:58+00:00","versionOfRecord":{"articleIdentity":"rs-101839","link":"https://doi.org/10.1186/s13048-021-00803-2","journal":{"identity":"journal-of-ovarian-research","isVorOnly":false,"title":"Journal of Ovarian Research"},"publishedOn":"2021-05-17 20:57:58","publishedOnDateReadable":"May 17th, 2021"},"versionCreatedAt":"2020-11-06 14:53:53","video":"","vorDoi":"10.1186/s13048-021-00803-2","vorDoiUrl":"https://doi.org/10.1186/s13048-021-00803-2","workflowStages":[]},"version":"v1","identity":"rs-101839","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-101839","identity":"rs-101839","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}