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Risk factors for the failure of first-line PARP inhibitor maintenance therapy in patients with advanced ovarian cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3004)

Kim, NK | Kim, Y | Kim, HS | Park, SJ | Hwang, DW | Lee, SJ | Yoo, JG | Chang, SJ  | Son, JH  | Kong, TW  | Kim, J  | Shim, SH | Lee, AJ | Suh, DH | Lee, YY
Cancer medicine, 12(19). : 19449-19459, 2023
Journal Title
Cancer medicine
Objective: To identify the risk factors for failure of first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer. Method: Patients with stage III-IV epithelial ovarian cancer who received first-line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups—recur/progression of disease (PD) and non-recur/PD. Results: In total, 191 patients were included. Median follow-up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non-high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre-PARPi serum CA-125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox-regression analysis revealed pre-PARPi serum CA-125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03–4.57; p = 0.042), non-HGSC (3.28; 1.20–8.97; p = 0.021), NAC (2.11; 1.04–4.26; p = 0.037), and no BRCA mutation (2.23; 1.12–4.44; p = 0.023) as independent risk factors associated with poor progression-free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre-PARPi serum CA-125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03–7.39; p = 0.044). Non-HGSC (5.05; 1.80–14.18; p = 0.002) and NAC (3.36; 1.25–9.04; p = 0.016) were independent risk factors in women without BRCA mutations. Conclusion: High pre-PARPi serum CA-125 levels, non-HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first-line PARPi maintenance therapy. In women with BRCA mutations, high pre-PARPi serum CA-125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.


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Journal Papers > School of Medicine / Graduate School of Medicine > Obstetrics & Gynecology
Ajou Authors
공, 태욱  |  김, 지연  |  손, 주혁  |  장, 석준
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