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)

Abstract

Abstract 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.

Keywords

• first‐line maintenance therapy
• ovarian cancer
• poly (ADP‐ribose) polymerase inhibitor
• recurrence
• risk factor