Real-world effectiveness and safety of olaparib in HRD-positive BRCA wild-type ovarian cancer

Ovarian cancer, a deadly gynecologic malignancy, has seen a significant shift in its treatment paradigm with the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors, which are now standard in the maintenance setting following first-line chemotherapy. This retrospective cohort study investigates the real-world effectiveness and safety of olaparib, a PARP inhibitor, in patients with newly diagnosed advanced-stage, high-grade serous ovarian cancer who are HRD positive but BRCA wild-type, a demographic less extensively explored in previous research. The primary goal was to assess the 1-year progression-free survival (PFS) rate of olaparib maintenance therapy in this specific patient group, offering insights into its potential as a therapeutic option.

Conducted across 11 high-volume tertiary care centers in China, the study included patients who received olaparib as frontline maintenance therapy after achieving a complete or partial response to platinum-based chemotherapy. The analysis focused on the 1-year PFS rate, median PFS, time to first subsequent therapy or death, and treatment-related adverse events. The 1-year PFS rate was 75.2%, with a median PFS of 21.0 months, aligning with previous trials and highlighting olaparib's efficacy in maintaining remission in patients with HRD-positive, BRCA wild-type ovarian cancer. The safety profile of olaparib was consistent with known adverse events, primarily anemia and nausea, with most patients continuing treatment without discontinuation due to these events.

The findings from this study are significant as they provide the first evidence supporting the use of olaparib in patients with newly diagnosed HRD-positive/BRCA wild-type ovarian cancer, a population that has been less studied in the context of PARP inhibitor efficacy. This fills a gap in the research and provides new therapeutic options for clinical treatment. Despite the study's limitations, including its retrospective design, short follow-up period, and small sample size, the results are still enlightening and require further validation through the ongoing phase III MONO-OLA1 study. Overall, this study underscores the importance of PARP inhibitors in the treatment of newly diagnosed ovarian cancer and offers a potential effective treatment option for HRD-positive/BRCA wild-type patients.