Neoadjuvant pamiparib in patients with newly diagnosed advanced ovarian cancer: A single-arm, prospective phase II trial.
Authors: Liu Jing , Hu Dan , Li Li , Zang Lele , Zhu Fei , Zhu Mingxuan , Zhang Huiqi , Chang Lele , Xu Qin 
Published: July 2024

e17555

Background: PARP inhibitors have been validated for their efficacy as maintenance therapy in newly diagnosed ovarian cancer, but their effectiveness as neoadjuvant therapy remains uncertain. The aim of this study is to explore the efficacy and safety of the combination of pamiparib with neoadjuvant chemotherapy and bevacizumab in patients with newly diagnosed ovarian cancer. Methods: This is a single-arm prospective phase II study that includes patients who meet the following criteria: newly diagnosed ovarian, fallopian tube, or peritoneal cancer with FIGO stages III-IV; histologically confirmed high-grade serous or endometrioid adenocarcinoma and ineligible for satisfactory debulking surgery. The treatment consists of paclitaxel 175mg/m2 on Day 1 and carboplatin AUC 5 on Day 2, every 3 weeks, for a maximum of 6 cycles. Bevacizumab is administered at a dose of 15mg/kg on Day 1, every 3 weeks, with discontinuation 6 weeks prior to surgery. Pamiparib is given at a dose of 40mg twice daily for a maximum of 6 cycles. Patients who tolerate the treatment and are deemed suitable for surgery undergo interval debulking surgery. After surgery, patients will receive consolidation and maintenance therapy based on the investigator's choice. The chemotherapy response score will be determined based on postoperative pathology evaluation. The primary endpoint was the proportion of patients with a Chemotherapy Response Score 3 (CRS 3). The second endpoints were proportion of patients with pathological complete response (pCR), proportion of patients with satisfactory debulking surgery (R0), progression-free survival (PFS) and safety. The trial is ongoing. Results: Between March 2023 and January 2024, thirteen patients with a median age of 60 years (range: 46 - 73), FIGO stage IIIB (1/13, 7.6%), IIIC (6/13, 46.2%) and IVB (6/13 46.2%) were enrolled. Among the 13 patients, 12 had high-grade serous adenocarcinoma, and 1 had endometrioid adenocarcinoma. 2 patients withdrew their informed consent after receiving 1 cycle of neoadjuvant therapy. Ten patients received four cycles of neoadjuvant therapy, while one patient received three cycles. 8 patients received interval debulking surgery and all of them achieved a R0 resection. Postoperative pathological evaluation showed ovarian CRS3 in 5 patients (62.5%), CRS2 in 2 patients (25%), and CRS1 in 1 patient (12.5%). All of these patients did not achieve a pCR. The most common adverse reactions were neutropenia (92.4%), leukopenia(92.4%), thrombocytopenia(77.0%), and anemia (100%), with grade 3-4 incidence rates of 76.1%, 53.7%, 30.7%, and 38.3%, respectively. No treatment-related death were observed. Conclusions: The combination of pamiparib with neoadjuvant chemotherapy and bevacizumab showed promising efficacy and acceptable toxicity in patients with newly diagnosed advanced ovarian cancer. We will report more data in the future. Clinical trial information: ChiCTR2200059119.