Efficacy And The Prognostic Factors Analysis Of Poly(ADP-ribose) Polymerase Inhibitors In The Treatment Of Recurrent Ovarian Epithelial Carcinoma

Background Ovarian cancer is a significant cause of cancer deaths in women.Epithelial ovarian cancer（EOC）accounts for 90%of ovarian cancer.The standard treatments for EOC include debunking surgery and platinum-based chemotherapy.However,over 80%of EOC patients relapse within 18 months and are resistant to chemotherapeutic treatment.Recurrent EOC has a lousy prognosis and limited treatment options.Recently,poly（ADP-ribose）polymerases inhibitor（PARPi）plays a key role in the treatment of EOC.The study focuses on the efficacy and prognostic factors of PARPi.It may bring good news to more patients with recurrent EOC.Objective The purpose of the study was to investigate the efficacy,safety and to explore possible prognostic factor of PARPi in the treatment of recurrent ovarian cancer in the real world.Methods This study collected the essential characteristics,pathological data,treatment process,imaging data,laboratory test results and adverse reactions of ovarian cancer patients who had received PARPi after recurrence in our hospital from January 2019 to October 2022.The relationships between different factors and progression-free survival（PFS）,objective response rate（ORR）,and disease control rate（DCR）were retrospectively analyzed.Based on the results,the possible prognostic factors of PARPi were discussed.The degree and incidence of adverse events were surveyed and analyzed.Results In this study,243 patients with recurrent ovarian cancer were screened,excluding patients who without pathological diagnosis,did not use PARPi after recurrence,and did not monitor CA125.Finally,36 patients with EOC who used PARPi after recurrence were included.The average age was 50 years.89.7%of patients were diagnosed with an advanced disease.Meaningful BRCA gene mutations were recorded in 10 patients.12,5,and 19 patients,respectively,were treated with PARPi as the second,third,fourth,or beyond.22 patients received PARPi as maintenance therapy after chemotherapy;2patients received PARPi in combination with other targeted agents,2 with immunotherapy,and the remaining 10 patients received PARPi alone.All patients receiving PARPi as maintenance therapy after chemotherapy were analyzed survival by treatment line number.Results showed that the median PFS was significantly longer in patients treated with PARPi on the second line compared with those treated with PARPi on the third or fourth line and above（13.43 months vs 3.770 months vs 5.37 months）,with a statistically significant difference in PFS between the second line and the fourth line and above（P=0.0238）.Second-line treatment was also better than third-line treatment,fourth-line treatment and above in OS（median OS 60.83 months vs47.5 months vs 36.2 months）,but the results were not statistically significant.According to the sensitivity to platinum at the time of relapse,patients were divided into the initial sensitive group and the primary platinum resistance group.The overall survival（OS）and the best efficacy of patients in the initial keen group after relapse were significantly better than those in the primary platinum-resistant group.The median PFS of the whole population was 5.37 months.Based on the sensitivity to platinum at the time of using PARPi,patients were divided into the P-sensitive group and the P-resistant group.ORR（44.4%vs 0%）,DCR（88.9%vs 55.6%）,and median PFS(6.67 months vs 2.27months,P<0.001^**)in the P-sensitive group were better than those in the P-resistant group.The p-resistance group was divided into the primary and secondary drug resistance groups according to the sensitivity to platinum at the time of relapse.The PFS in the primary resistance group was slightly better than that in the secondary resistance group,but the results were not statistically significant（P=0.503）.The receiver operator characteristic curves of carbohydrate antigen 125（CA125）value at initial diagnosis,the last serum CA125 value before PARPi treatment,and the lowest CA125 value during previous chemotherapy were respectively made.The optimal cut-off values of the three-time nodes were determined,which were 96.54,75.92,and22.75 respectively.In univariate analysis,the number of treatment lines,combination regimen,platinum sensitivity at recurrence,platinum sensitivity at the time of using PARPi,and the lowest CA125 value in previous chemotherapy were significantly correlated with PFS.Platinum sensitivity using PARPi was an independent prognostic factor for PFS in multivariate analysis（P=0.018）.28 patients suffered drug-related adverse reactions during treatment.Fatigue was the most common adverse reaction（41.7%）,while anemia was the most common and most specific severe adverse reaction（44.4%）.Conclusions Firstly,early use of PARPi may reduce the risk of patient progression.PARPi as a maintenance treatment after chemotherapy can bring better benefits to patients.Secondly,a platinum-resistant ovarian cancer patient’s prognosis is significantly worse than that of a platinum-sensitive patient.The sensitivity of the patient to platinum at the time of using PARPi is a critical factor affecting the efficacy of PARPi.Finally,the lowest serum CA125 value during previous chemotherapy was a predictor of PARPi efficacy,and the lower value was associated with a longer PFS.These results can provide a reference for the clinical formulation of individualized treatment plans for EOC.