Real-world efficacy and safety data of the use of PARP inhibitors in advanced ovarian cancer: the experience of the Hellenic Cooperative Oncology Group

Background: Real-world data regarding the use of poly (ADP (adenosine phosphate)-ribose) polymerase inhibitors (PARPi) or bevacizumab as maintenance treatment in patients with ovarian cancer (OVCA) is critical in everyday therapeutic decision-making. Our aim was to assess clinical outcomes and adverse events of different maintenance regimens after first- and second-line in patients with OVCA. Methods: This was a retrospective-prospective multi-center observational study including patients recorded in the Hellenic Cooperative Oncology Group (HeCOG) electronic database. Patients were diagnosed with advanced stage, high grade ovarian, primary peritoneal and fallopian tube cancer. Patient demographics, tumor clinicopathologic, germline and tumor molecular data, clinical outcome and toxicity data were recorded. The primary endpoint was progression-free survival (PFS1) from the initiation from first-line treatment. Results: From 11 January 2019 to 09 March 2023, 185 patients with advanced OVCA were identified; median age 56.4. Overall, 120 (64.9%) patients received maintenance treatment after first-line (55.0% received bevacizumab and 37.5% PARPi, predominantly olaparib), while 96 (51.9%) after second-line treatment (mostly olaparib, 78.1%). Notably, 87 (47%) patients received maintenance therapy following both lines of treatment. Germline alterations were identified in 53.7% of patients. Maintenance therapy with either PARPi or bevacizumab significantly improved PFS in both first-line (p < 0.001) and second-line (p < 0.001) treatment compared to no maintenance. No difference in overall survival was observed between patients receiving maintenance treatment vs. those who did not (p = 0.590). Most common adverse events with olaparib were anaemia (41%), leukopenia (22.2%), fatigue (17.1%) and thrombocytopenia (13.7%). No differences were found in the rate of adverse events between patients >65 years of age and younger patients. Conclusions: Real-world evidence supports the efficacy of PARPi in improving PFS in advanced OVCA, aligning with clinical trial findings. Early molecular and genetic testing is critical for optimal treatment selection. Further studies evaluating the optimal sequencing and long-term outcomes of maintenance therapies are warranted.

Germline testing; Molecular testing; Ovarian cancer; Outcomes; PARP inhibitor; Olaparib; Niraparib; Progression-free survival

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