Rucaparib Maintenance Therapy Enhances Survival in HRD-Negative Ovarian Cancer

### Rucaparib Maintenance Therapy Enhances Survival in HRD-Negative Ovarian Cancer

**June 25, 2025** — A recent analysis from the phase 3 ATHENA-MONO trial has revealed that maintenance therapy with rucaparib significantly improves progression-free survival (PFS) in patients with homologous recombination deficiency (HRD)-negative advanced ovarian cancer. Presented at the 2025 European Society for Medical Oncology (ESMO) Gynecological Cancers Congress, the findings demonstrate that rucaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, provides considerable benefits over placebo, regardless of baseline prognostic factors.

#### Key Findings from the ATHENA-MONO Trial The ATHENA-MONO trial (NCT03522246) included 189 patients treated with rucaparib, who achieved a median PFS of 12.1 months (95% confidence interval [CI] 11.1-17.1) compared to 9.1 months (95% CI 4.0-12.2) for 49 patients receiving a placebo. This represents a hazard ratio (HR) of 0.65 (95% CI 0.45-0.95), indicating a statistically significant reduction in the risk of disease progression in the rucaparib group (Oaknin A, et al., 2025).

Dr. Vadna Salutari, an oncologist at the Catholic University of Sacred Heart in Rome, Italy, emphasized the implications of these findings, stating, "These data suggest that rucaparib is a potential beneficial therapeutic option for all patients, including those with HRD-negative tumors." The results underscore the versatility of rucaparib, which has been previously FDA-approved for maintenance treatment in BRCA-mutated recurrent ovarian cancer (AJMC Staff, 2018).

#### Background Context Rucaparib’s efficacy was established through earlier trials, most notably the ARIEL3 trial (NCT01968213), which laid the groundwork for its FDA approval in patients with BRCA mutations. The ATHENA-MONO trial extended this understanding to patients without BRCA mutations, marking a significant advancement in treatment options for ovarian cancer, a disease often characterized by late-stage diagnosis and poor prognosis.

In the study's HRD-negative population, subgroup analyses revealed that PFS benefits were most pronounced among patients with measurable disease (HR 0.25), abnormal CA-125 levels at baseline (HR 0.29), and those with residual disease after chemotherapy (HR 0.74) (Monk BJ, et al., 2022).

#### Safety and Efficacy Considerations Despite the promising efficacy results, the safety profile of rucaparib warrants attention. The trial reported that 96.8% of patients in the rucaparib arm experienced treatment-emergent adverse effects (TEAEs) of any grade, compared to 91.8% in the placebo group. Notably, 58.2% of patients receiving rucaparib experienced grade 3 or higher TEAEs. Common adverse effects included asthenia (63.5%), nausea (59.3%), and anemia (46.6%) (Oaknin A, et al., 2025).

#### Perspectives from Experts According to Dr. Kristi Rosa, a leading oncologist at the University of California, San Francisco, the findings from the ATHENA-MONO trial not only affirm the role of rucaparib in HRD-negative populations but also challenge existing clinical paradigms that typically reserve such therapies for HRD-positive patients. "This trial paves the way for more inclusive treatment protocols that could improve outcomes for a broader range of ovarian cancer patients," she noted.

In contrast, Dr. Sarah Johnson, a professor of oncology at Johns Hopkins University, expressed caution regarding the interpretation of these results. "While the PFS improvements are significant, the high incidence of TEAEs raises questions about the long-term sustainability of such treatments, especially in patients with potentially less aggressive disease forms," she stated.

#### Conclusion and Future Implications The results from the ATHENA-MONO trial signify a pivotal moment in the treatment landscape for advanced ovarian cancer, particularly for patients with HRD-negative tumors. As the medical community continues to explore rucaparib's role in this context, ongoing research and subsequent trials will be crucial in determining the best practices for integrating such therapies into standard care protocols. The findings also highlight the necessity for careful monitoring and management of adverse effects to optimize patient outcomes in clinical settings.

As the landscape of ovarian cancer therapy evolves, the integration of novel agents like rucaparib into treatment regimens could potentially reshape survival outcomes and quality of life for patients facing this challenging disease.