Rucaparib Maintenance Yields PFS Benefit Across HRD-Negative Subgroups of High-Grade Ovarian Cancer

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First-line maintenance therapy with rucaparib (Rubraca) is effective across subgroups of patients with advanced, high-grade ovarian cancer, including those with homologous recombination–deficient (HRD)–negative disease, according to Vanda Salutari, MD.

“In the ATHENA-MONO [arm of the phase 3 ATHENA trial (NCT03522246)], first-line rucaparib maintenance provided a sustained progression-free survival [PFS] benefit vs placebo in newly diagnosed, advanced high-grade ovarian cancer after frontline platinum-based chemotherapy,” Salutari summarized in an interview with OncLive®.

Among all patients with HRD-negative disease, the median investigator-assessed PFS was previously reported to be 12.1 months (95% CI, 11.1-17.7) with rucaparib (n = 189) vs 9.1 months (95% CI, 4.0-12.2) with placebo (n = 49; HR, 0.65; 95% CI, 0.45-0.95).1,2 Findings from subgroup analyses presented at the 2025 ESMO Gynecological Cancers Congress showed that PFS outcomes favored rucaparib across all prespecified patient subgroups, including patients with measurable disease at baseline (HR, 0.25; 95% CI, 0.08-0.80), patients with above-normal CA-125 levels at baseline (HR, 0.29; 95% CI, 0.10-0.84), and those with residual disease post-chemotherapy (HR, 0.38; 95% CI, 0.19-0.79).2

In the interview, Salutari discussed the importance of determining the efficacy of first-line rucaparib maintenance therapy in patients with HRD-negative ovarian cancer following responses to frontline platinum-based chemotherapy, elaborated on the clinical implications of the efficacy findings from ATHENA-MONO, and highlighted anticipated next steps for this research.

Salutari is an oncologist in the Department of Health of Woman and Child, at the Catholic University of Sacred Heart in Rome, Italy.

OncLive: What was the rationale for the ATHENA-MONO trial?

Salutari: The largest subgroup of patients in ATHENA-MONO had HRD-negative disease. These patients were BRCA wild-type with low loss of heterozygosity [LOH]; in the study, the test used [to assess tumor HRD status] was the FoundationOne CDx assay, with the [low] LOH cutoff [defined as levels] less than 16%. The HRD population is usually associated with worse prognosis, [including] worse PFS and overall survival [OS] compared with the BRCA-mutated or HRD-positive population. In this context, a clinically effective maintenance treatment is an important unmet need.

What was the design of the ATHENA trial and the ATHENA-MONO arm of the trial?

ATHENA-MONO is a part of a study that included 4 arms. ATHENA-MONO is a comparison between rucaparib and placebo in patients with advanced stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Inclusion criteria were that patients must have completed frontline platinum doublet chemotherapy and surgery and achieved a complete or partial response; [patients must have also undergone] cytoreductive surgery [in the] primary or interval debulking [settings]. [ECOG] performance status [needed to] be 0 or 1, and no prior frontline maintenance treatment for ovarian cancer could have been received by this population.

[Patients in] this population were randomly assigned to receive rucaparib at 600 mg twice daily orally vs placebo. Stratification factors included 2 or more HRD test status. Other stratification factors were disease status post-chemotherapy and timing of surgery. Patient received rucaparib for 2 years or until progression of disease or toxicity.

What key efficacy findings with rucaparib were observed in the ATHENA-MONO HRD-negative patient population?

ATHENA-MONO showed in the HRD-negative population a clinically significant benefit in PFS in patients receiving rucaparib vs placebo. The HR was 0.65, and the median PFS was 12.1 months in patients receiving rucaparib vs 9.1 months in patients receiving placebo. These results, in my opinion, are clinically significant because they mean that patients receiving rucaparib have a reduction in the risk of progression of 35%.

What is important to note about the safety findings from the HRD-negative population of ATHENA-MONO?

Regarding toxicity, no new signals were detected in the HRD-negative population. Hematological toxicities, increases in alanine aminotransferase and aspartate aminotransferase levels, asthenia, and nausea were confirmed to be the most common adverse effects [observed with rucaparib].

How might the ATHENA-MONO data influence the future role of rucaparib in ovarian cancer management?

This study [showed] that maintenance treatment with rucaparib is an effective treatment in patients with advanced cancer who responded after first-line chemotherapy, [as well as] in patients with residual disease after chemotherapy, measurable disease, and abnormal CA-125 [levels] at baseline. The next step [in this research] is a longer follow-up, as well as [reporting] the OS data. I hope the results presented at [the 2025 ESMO Gynecological Cancers Congress] will be confirmed in this term.

References

  1. Monk BJ, Parkinson C, Lim MC, et al. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40(34):3952-3964. doi:10.1200/JCO.22.01003
  2. Oaknin A, Prendergast E, Salutari V, et al. Efficacy and safety of rucaparib maintenance treatment in patients from ATHENA-MONO/GOG-3020/ENGOT-OV45 with newly diagnosed advanced ovarian cancer not associated with homologous recombination deficiency. Ann Oncol. 2025;10(suppl 5):105204. doi:10.1016/j.esmoop.2025.105204

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