Study On The Role Of PARP Inhibitors In The Treatment Of PALB2 Mutation Platinum-sensitive Recurrent Ovarian Cancer

Objective:To evaluate the progression-free survival of patients with PALB2-mutated and BRCA-mutated in platinum-sensitive recurrent epithelial ovarian cancer after oral Poly ADP-ribose Polymerase(PARP)inhibitor therapy and the prognostic factors affecting PFS.Methods:Patients with platinum-sensitive recurrent epithelial ovarian cancer diagnosed in Shanxi Provincial Cancer Hospital from January 2019 to July 2021 were selected.A total of 43 eligible patients with platinum-sensitive recurrent epithelial ovarian cancer who oral PARP inhibitor(olaparib)were enrolled.The general data of all enrolled patients were collected,and the time of starting oral olaparib maintenance therapy was recorded.The genetic testing results of the enrolled patients were counted.In this study,a total of19 patients were enrolled from patients who underwent only BRCA1/2 gene testing,including 11 BRCA mutation and 8 non-BRCA mutation.A total of 24 patients were included in the whole gene test,including 12 patients with BRCA mutation,10 patients with HRD-negative(included in non-BRCA mutation group for study),and 2 patients of PALB2 mutation.Therefore,there were 23 patients in the BRCA mutation group and 18 patients in non-BRCA mutation group in this study.The survival status of patients in each group at the time of data cutoff was counted through follow-up,and the time from the beginning of oral olaparib tablets to disease recurrence was recorded.The PFS of patients in each group after oral olaparib tablets maintenance treatment was analyzed,and the prognostic factors were analyzed.Results:1.Mutation types of PALB2 in this study: p.T51 Qfs Ter2(frameshift mutation),c.3114-1G>A(possible pathogenic variant).The mutation rate of PALB2 in this study was 1.4%.2.There was no significant difference in the baseline data between the BRCA mutantion group and the non-mutated group included in the patients who underwent BRCA1/2 gene testing and full gene testing;There were no statistically significant differences in baseline data among the BRCA mutantion group,HRD negative group,and PALB2 mutantion group.3.From the patients who underwent BRCA1/2 gene testing and whole gene testing,patients in the BRCA mutantion group had longer PFS after oral olaparib maintenance therapy compared with non-BRCA mutation group.4.The patients who underwent whole gene testing were divided into PALB2 mutantion group,BRCA mutantion group and HRD negative group according to the test results.PFS of patients in the three groups were 11 months,13 months and 10 months respectively,with no statistical significance(P > 0.05).5.Analysis of the risk factor of PFS after oral olaparib in BRCA mutantion and non-mutated patients included in the BRCA1/2 gene testing and whole gene testing according to the test results,shows that the number of previous chemotherapy lines is independent risk factors after oral olaparib maintenance therapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.Conclusion:1.Patients with platinum-sensitive recurrent epithelial ovarian cancer with BRCA gene mutation have better maintenance treatment effect with oral olaparib tablets than patients without BRCA gene mutation;the mutation rate of PALB2 in this study was only1.4%,BRCA gene mutation and PALB2 mutation patients had longer PFS than HRD negative group,but the difference was not statistically significant.2.The number of previous chemotherapy lines is an independent prognostic factor after oral olaparib maintenance therapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.3.The efficacy of oral PARP inhibitors in patients with platinum-sensitive recurrent epithelial ovarian cancer is not only related to BRCA1/2 genes and homologous recombination repair genes,but also affected by gene mutations in other homologous recombination repair pathways,and more effective target genes need to be identified.