Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer
ObjectiveThe current clinical data regarding the re-administration of PARPi maintenance therapy in platinum sensitive recurrent ovarian cancer (PSROC) is limited. This study aims to investigate the efficacy and associated factors of PARPi re-maintenance therapy in PSROC patients in China.MethodsIn t...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1512339/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841549944908939264 |
|---|---|
| author | Yulin Wang Yunjie Yang Binghong Guo Binghong Guo Xiaoyan Li Renakezi Tuersun Ye Cao Jundong Li Jihong Liu Su Li Tao Liu Yongwen Huang |
| author_facet | Yulin Wang Yunjie Yang Binghong Guo Binghong Guo Xiaoyan Li Renakezi Tuersun Ye Cao Jundong Li Jihong Liu Su Li Tao Liu Yongwen Huang |
| author_sort | Yulin Wang |
| collection | DOAJ |
| description | ObjectiveThe current clinical data regarding the re-administration of PARPi maintenance therapy in platinum sensitive recurrent ovarian cancer (PSROC) is limited. This study aims to investigate the efficacy and associated factors of PARPi re-maintenance therapy in PSROC patients in China.MethodsIn this study, there were 201 patients with PSROC who had received maintenance therapy previously and achieved complete or partial response after platinum-based chemotherapy upon recurrence. The re-maintenance therapy group (Re-PARPi) and chemotherapy alone group (Chem-A) were categorized based on whether PARPi was reused after recurrence chemotherapy. A propensity-score matching (PSM) analysis was conducted between re-maintenance therapy group (Re-PARPi-P) and chemotherapy alone group(Chem-A-P)to adjust for imbalanced risk factors. The efficacy was evaluated via progression-free survival (PFS) and prognostic factors were also analyzed.ResultsIn the PSM subgroup, the median PFS (mPFS) of Re-PARPi-P group (44 cases) and Chem-A-P (44 cases) group were 10.0 months and 6.5 months (HR 1.64, P=0.041) respectively, confirming that re-maintenance therapy was superior to relapse chemotherapy alone. The mPFS was 10.8 months in all patients in the Re-PARPi group (51 cases), with 11.0 months in BRCAm group and 10.2 months in BRCAwt group (P=0.806). Intervals of more than 6 months between two PARPi therapies might improve the efficacy of PARPi re-treatment (mPFS 11.2 months vs. 7.8 months, HR 3.94, P=0.005). Age, BRCA status, number of previous treatment lines, CA125 level prior to re-administration, and other factors were not significantly related to the efficacy of re-maintenance therapy. Patients with a frameshift mutation (p. Ile1824Aspfs3) in the C-terminal domain of BRCA1 germline gene had significantly better efficacy with PARPi re-treatment compared to other groups. Only nonsense mutation (p.Gln1037, p.Cys328, p.Leu1072) occur in BRCA germline gene with re-treatment with PARPi might be suboptimal. The incidence of PARRi re-treatment interruption was 3.9%.ConclusionPARPi re-maintenance therapy in PSROC might improve prognosis compared to chemotherapy alone, regardless of their genetic mutation status. Patients with re-maintenance therapy might benefit if the interval between the use of PARP inhibitors exceeded 6 months. The structural domains of BRCA mutations with different sensitivity to PARPi might serve as a promising biomarker for optimizing treatment. Re-treatment with PARPi was well-tolerated. |
| format | Article |
| id | doaj-art-a0c69caaf1334e26874b7b3f3d8e8b30 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-a0c69caaf1334e26874b7b3f3d8e8b302025-01-10T11:36:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15123391512339Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancerYulin Wang0Yunjie Yang1Binghong Guo2Binghong Guo3Xiaoyan Li4Renakezi Tuersun5Ye Cao6Jundong Li7Jihong Liu8Su Li9Tao Liu10Yongwen Huang11State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Clinical Pharmacology, Guangdong Pharmaceutical University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Gynecological Oncology, Cancer Hospital of Shantou University Medical College, Shantou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Gynecology, The First People’s Hospital of Kashi, Kashi, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaObjectiveThe current clinical data regarding the re-administration of PARPi maintenance therapy in platinum sensitive recurrent ovarian cancer (PSROC) is limited. This study aims to investigate the efficacy and associated factors of PARPi re-maintenance therapy in PSROC patients in China.MethodsIn this study, there were 201 patients with PSROC who had received maintenance therapy previously and achieved complete or partial response after platinum-based chemotherapy upon recurrence. The re-maintenance therapy group (Re-PARPi) and chemotherapy alone group (Chem-A) were categorized based on whether PARPi was reused after recurrence chemotherapy. A propensity-score matching (PSM) analysis was conducted between re-maintenance therapy group (Re-PARPi-P) and chemotherapy alone group(Chem-A-P)to adjust for imbalanced risk factors. The efficacy was evaluated via progression-free survival (PFS) and prognostic factors were also analyzed.ResultsIn the PSM subgroup, the median PFS (mPFS) of Re-PARPi-P group (44 cases) and Chem-A-P (44 cases) group were 10.0 months and 6.5 months (HR 1.64, P=0.041) respectively, confirming that re-maintenance therapy was superior to relapse chemotherapy alone. The mPFS was 10.8 months in all patients in the Re-PARPi group (51 cases), with 11.0 months in BRCAm group and 10.2 months in BRCAwt group (P=0.806). Intervals of more than 6 months between two PARPi therapies might improve the efficacy of PARPi re-treatment (mPFS 11.2 months vs. 7.8 months, HR 3.94, P=0.005). Age, BRCA status, number of previous treatment lines, CA125 level prior to re-administration, and other factors were not significantly related to the efficacy of re-maintenance therapy. Patients with a frameshift mutation (p. Ile1824Aspfs3) in the C-terminal domain of BRCA1 germline gene had significantly better efficacy with PARPi re-treatment compared to other groups. Only nonsense mutation (p.Gln1037, p.Cys328, p.Leu1072) occur in BRCA germline gene with re-treatment with PARPi might be suboptimal. The incidence of PARRi re-treatment interruption was 3.9%.ConclusionPARPi re-maintenance therapy in PSROC might improve prognosis compared to chemotherapy alone, regardless of their genetic mutation status. Patients with re-maintenance therapy might benefit if the interval between the use of PARP inhibitors exceeded 6 months. The structural domains of BRCA mutations with different sensitivity to PARPi might serve as a promising biomarker for optimizing treatment. Re-treatment with PARPi was well-tolerated.https://www.frontiersin.org/articles/10.3389/fonc.2024.1512339/fullrecurrent ovarian cancerPARP inhibitorsre-maintenance therapyprognosisstructural domains of BRCA mutations |
| spellingShingle | Yulin Wang Yunjie Yang Binghong Guo Binghong Guo Xiaoyan Li Renakezi Tuersun Ye Cao Jundong Li Jihong Liu Su Li Tao Liu Yongwen Huang Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer Frontiers in Oncology recurrent ovarian cancer PARP inhibitors re-maintenance therapy prognosis structural domains of BRCA mutations |
| title | Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer |
| title_full | Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer |
| title_fullStr | Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer |
| title_full_unstemmed | Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer |
| title_short | Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer |
| title_sort | efficacy of parpi re maintenance therapy for recurrent ovarian cancer |
| topic | recurrent ovarian cancer PARP inhibitors re-maintenance therapy prognosis structural domains of BRCA mutations |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1512339/full |
| work_keys_str_mv | AT yulinwang efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT yunjieyang efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT binghongguo efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT binghongguo efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT xiaoyanli efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT renakezituersun efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT yecao efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT jundongli efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT jihongliu efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT suli efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT taoliu efficacyofparpiremaintenancetherapyforrecurrentovariancancer AT yongwenhuang efficacyofparpiremaintenancetherapyforrecurrentovariancancer |