Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups

Abstract

BackgroundPoly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.Primary ObjectiveTo determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.Study HypothesisOlaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.Trial DesignPhase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator’s choice.Major Eligibility CriteriaEligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.Primary EndpointThe dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.Sample SizeApproximately 200 patients will be enrolled in this study.Estimated Dates for Completing Accrual and Presenting ResultsEnrollment will be completed in 2024. Results will be presented in 2026.Trial RegistrationEudraCT 2021-000245-41 NCT05255471

[Retracted] Clinical Efficacy and Safety of Tumor Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy for Ovarian Cancer

“…In the present study, the experimental group had a higher ORR and shorter duration of postoperative chemotherapy, length of hospital stay, and a lower 1-year postoperative disease recurrence rate than the observation Evidence-Based Complementary and Alternative Medicine group, suggesting that HIPEC after CRS efectively enhances the clinical outcome and postoperative recovery of ovarian cancer patients and reduces their risk of disease recurrence. Tis is because intraperitoneal hyperthermic perfusion chemotherapy can greatly increase the tissue penetration of chemotherapeutic drugs and improve its anti-tumor efect; it can also kill heat-sensitive G0 cells, resulting in clinical benefts [20]. VEGF is a provascular endothelial cell growth factor including several isoforms; VEGFA and VEGFB have the efect of inducing neovascularization, while VEGFC induces lymphangiogenesis.…”

Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer: lessons learned and future directions

“…Larger-scale prospective research is warranted to shed more light on the role of PARPi rechallenge, which might change the treatment algorithm of ovarian cancer in the future. The phase III randomized MITO 35b trial is currently investigating the use of olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in recurrent ovarian cancer patients 51. Since PARPi are not all the same but display different chemical structures, targets, and trapping potency, it would also be worth exploring the clinical impact of rechallenging with a different PARPi agent than the one used previously.…”