Marta Ostrowska-Leśko

Advances in Systemic Therapy for Ovarian Cancer Over the Past Decade: A Clinical and Molecular Perspective

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality, with high rates of recurrence and chemoresistance. Advances in understanding the molecular biology of EOC, particularly BRCA mutations and homologous recombination deficiency (HRD), have led to more targeted therapies. This review provides an updated summary of systemic treatments for EOC, with an emphasis on personalized therapy approaches and emerging therapeutic strategies. This review synthesizes current research and clinical trials investigating molecular pathways in EOC, particularly focusing on HRD, BRCA status, and their impact on treatment selection, including the use of PARP inhibitors, chemotherapy, and immunotherapy. Recent studies demonstrate that PARP inhibitors, particularly in patients with BRCA mutations or HRD-positive tumors, have resulted in improved progression-free survival. Ongoing trials combining PARP inhibitors with immunotherapy and angiogenesis inhibitors show promise in extending treatment efficacy and overcoming resistance mechanisms. Despite these advances, recurrence remains common among patients with advanced ovarian cancer. The integration of genetic and molecular insights into systemic treatment is crucial in advancing the management of EOC. While targeted therapies have significantly improved patient outcomes, further research is necessary to optimize treatment strategies and address therapeutic resistance, particularly in patients with non-BRCA-mutated EOC. The future of EOC treatment lies in refining personalized therapies and improving predictive biomarkers for better patient selection.

Optimizing bevacizumab dosing in first-line ovarian cancer treatment: the PGOG-ov1 trial

The management of advanced ovarian cancer has significantly developed with the integration of bevacizumab into standard therapeutic regimens. While the efficacy of bevacizumab has been established in trials such as GOG218, ICON7, and PAOLA-1, there remains a gap in understanding the advantages of the 7.5 mg/kg dose over the 15 mg/kg regimen. This study addresses this gap by evaluating the efficacy, safety, and cost effectiveness of these two dosing strategies, considering the heterogeneity of patient profiles, including BRCA mutation status and homologous recombination deficiency (HRD). This multicenter, randomized clinical trial will recruit patients with newly diagnosed, advanced-stage (FIGO III/IV) ovarian, fallopian tube, or primary peritoneal cancer. Participants will undergo three cycles of neoadjuvant chemotherapy with bevacizumab, followed by interval debulking surgery and randomization into four treatment arms stratified by BRCA and HRD status. Patients will receive either 7.5 mg/kg or 15 mg/kg bevacizumab in combination with chemotherapy during the adjuvant treatment phase and continue with maintenance therapy for up to 64 weeks, with or without the addition of olaparib. The primary endpoint is progression-free survival. The secondary endpoints include the overall response rate, quality of life, and safety profile. Data analysis focuses on subgroup evaluation of the influence of BRCA and HRD status on treatment outcomes. This study is expected to provide critical insights into optimizing bevacizumab dosing, potentially enabling the inclusion of cost-effective and safer treatment protocols without compromising efficacy. TRIAL REGISTRATION: EUCT number: 2023-509659-15-00. Registered on 09.07.2024.