Neoadjuvant pamiparib in patients with newly diagnosed advanced ovarian cancer: A single-arm, prospective phase II trial.

Abstract

5593 Background: While PARP inhibitors have shown robust efficacy as maintenance therapy in newly diagnosed ovarian cancer, their potential benefit in the neoadjuvant setting remains unclear. The Chemotherapy Response Score (CRS) serves as an important prognostic indicator following neoadjuvant chemotherapy. This study aims to investigate the efficacy and safety of combining pamiparib with neoadjuvant chemotherapy and bevacizumab in patients with newly diagnosed advanced ovarian cancer. Methods: In this single-arm, prospective phase II trial, eligible patients have newly diagnosed FIGO stage III–IV ovarian, fallopian tube, or primary peritoneal cancer; histologically confirmed high-grade serous or endometrioid adenocarcinoma; are ineligible for optimal primary debulking; have an ECOG performance status of 0–2; are aged ≥18 years; and have measurable lesions per RECIST 1.1. The treatment regimen comprises paclitaxel (175 mg/m^2, Day 1) and carboplatin (AUC 5, Day 2) every three weeks for up to six cycles. Bevacizumab (15 mg/kg, Day 1) is given every three weeks and discontinued six weeks before surgery. Pamiparib (40 mg twice daily) is administered for up to six cycles. Patients who tolerate therapy and become surgical candidates undergo interval debulking surgery, followed by consolidation and maintenance therapy at the investigator’s discretion. The primary endpoint is the proportion of patients with CRS 3, assessed via postoperative pathology. Secondary endpoints include the pathological complete response (pCR) rate, the R0 resection rate, progression-free survival (PFS), and safety. The trial is ongoing. Results: Between March 2023 and January 2025, 29 patients (median age 61 years, range 44–79) were enrolled. FIGO stages were III in 19 patients (65.5%), IVA in 1 (3.4%), and IVB in 9 (31.0%). Of these, 28 had high-grade serous adenocarcinoma and 1 had endometrioid adenocarcinoma. Two patients withdrew consent after receiving one cycle of neoadjuvant therapy. Of the remaining 27, 17 received four cycles, 7 received three cycles, and 3 received two cycles. Interval debulking surgery was performed in 24 patients—all achieved R0 resection—while 2 patients declined surgery and 1 had the treatment regimen changed due to elevated CA125. Among the 24 surgical cases, CRS 3 was observed in 8 (34.8%), CRS 2 in 15 (65.2%), and CRS 1 in 1 (4.3%). No patient achieved pCR. Common adverse events included leukopenia (96.6%), neutropenia (96.6%), anemia (96.6%), and thrombocytopenia (72.4%), with grade 3–4 incidences of 58.6%, 72.4%, 27.6%, and 24.1%, respectively. No treatment-related deaths were reported. Conclusions: The preliminary results suggest that the addition of pamiparib to neoadjuvant chemotherapy plus bevacizumab offers promising efficacy and acceptable safety in newly diagnosed advanced ovarian cancer. Further data will be provided as the study progresses. Clinical trial information: 2200059119 .