First trial of chemotherapy de-escalation in ovarian cancer (OC): A phase III randomized, open label study of niraparib maintenance after carboplatin and paclitaxel in patients with optimally debulked advanced (homologous recombination deficient) HRD high-grade ovarian cancer in first line therapy (N-PLUS/NOGGO-ov53/ENGOT-ov62).

person Elena Ioana Braicu Charite-Universitätsmedizin Berlin, Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum and North-Eastern German Society of Gynaecological Oncology (NOGGO) and Stanford University, Berlin, Germany info_outline Elena Ioana Braicu, Klaus Pietzner, Dario Zocholl, Purificación Estévez-García, Dionyssios Katsaros, Toon Van Gorp, Regina Berger, Maren Keller, Jalid Sehouli

Authors person Elena Ioana Braicu Charite-Universitätsmedizin Berlin, Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum and North-Eastern German Society of Gynaecological Oncology (NOGGO) and Stanford University, Berlin, Germany info_outline Elena Ioana Braicu, Klaus Pietzner, Dario Zocholl, Purificación Estévez-García, Dionyssios Katsaros, Toon Van Gorp, Regina Berger, Maren Keller, Jalid Sehouli Organizations Charite-Universitätsmedizin Berlin, Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum and North-Eastern German Society of Gynaecological Oncology (NOGGO) and Stanford University, Berlin, Germany, Charite-Universitätsmedizin Berlin, Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum and North-Eastern German Society of Gynaecological Oncology (NOGGO), Berlin, Germany, Institute for Biometry and Clinical Epidemiology, Charité-University Medicine of Berlin and North-Eastern German Society of Gynaecological Oncology (NOGGO), Berlin, Germany, Hospital Universitario Virgen del Rocío, Medical Oncology Department, and GEICO, Seville, Spain, Sant'Anna Hospital and MaNGO, Torino, Italy, University Hospital Leuven, Leuven Cancer Institute and BGOG, Leuven, Belgium, Medical University of Innsbruck, Department for Gynecology and Obstetrics, and AGO-Austria, Innsbruck, Austria, North-Eastern German Society of Gynaecological Oncology (NOGGO), Berlin, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company GSK Background: OC is the fifth most common cause of death from cancer in women. More than 70% of the patients are diagnosed with advanced disease and less than 40% of women with OC are cured. Currently, the standard therapy in HRD OC is surgical debulking followed by 6 cycles of chemotherapy with subsequent maintenance treatment with poly ADP ribose polymerase (PARP) inhibitors. Within the last decades, no focus was set on the benefits of fewer cycles of chemotherapy, even though there is evidence for comparable efficacy and less toxicity in comparison to more cycles. Chemotherapies are usually associated with side effects, which can be severe and even lead to therapy discontinuation. The data available about the needed number of chemotherapy cycles is weak, especially in the context of PARP inhibition. Furthermore, patients with stage III/IV with optimal cytoreduction are underrepresented in previous studies. In the N-PLUS trial, we hypothesize that recurrence-free survival (RFS) in patients receiving 3 cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRD high-grade OC patients with no visible disease following primary tumor debulking. Methods: In this multicenter, randomized, open-label study 650 patients with advanced HRD high-grade OC with no residual tumor mass following primary tumor debulking will be enrolled. Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B) for a maximum of 36 months. Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm/LOH-independent or BRCAwt/LOHhigh, FIGO stage III vs. IV, and participating countries. The primary endpoint will be RFS, secondary endpoints will be OS, TFST, TWIST, PFS2, Quality of Life and safety assessments. Clinical trial information: NCT05460000.

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