First-Line Rucaparib Maintenance Reduces Progression Risk Across Prognostic Subgroups in HRD– High-Grade Ovarian Cancer

Rucaparib Maintenance in HRD-Negative
Ovarian Cancer | Image Credit: © magicmine -
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Findings from an analysis of the phase 3 ATHENA-MONO arm of the ATHENA trial (NCT03522246) demonstrated that first-line maintenance with rucaparib (Rubraca) was associated with PFS improvements vs placebo in patients with homologous recombination deficiency (HRD)–negative ovarian cancer, irrespective of prognostic factors.1

Data presented at the 2025 ESMO Gynecological Cancers Congress showed that patients treated with rucaparib (n = 189) achieved a median progression-free survival (PFS) of 12.1 months (95% CI, 11.1-17.1) per investigator assessment compared with 9.1 months (95% CI, 4.0-12.2) for those given placebo (n = 49; HR, 0.65; 95% CI, 0.45-0.95).

“[Regard] the subgroup analyses of this HRD-negative population, we can see that the [PFS] benefit is felt across most of the subgroups, but mostly in patients with measurable disease [HR, 0.25; 95% CI, 0.08-0.80], abnormal CA-125 at baseline [HR, 0.29; 95% CI, 0.10-0.84], and residual disease after chemotherapy [HR, 0.74; 95% CI, 0.47-1.15],” presenting study author Vadna Salutari, MD, of the Catholic University of Sacred Heart in Rome, Italy, said during the presentation.

Rucaparib is currently approved by the FDA for the maintenance treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)–associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.2 That regulatory decision was supported by data from the phase 3 ARIEL3 trial (NCT01968213).

“These data [from ATHENA-MONO] suggest that rucaparib is a potential beneficial therapeutic option for all patients, including those with HRD-negative tumors,” Salutari said.

ATHENA Background

Previously reported from ATHENA-MONO showed that in the trial’s HRD-positive population, patients treated with rucaparib (n = 185) achieved a median PFS of 28.7 months (95% CI, 23.0-not reached [NR]) per investigator assessment vs 11.3 months (95% CI, 9.1-22.1) for those given placebo (n = 49; HR, 0.47; 95% CI, 0.31 to 0.72; log-rank P = .0004).2 In the study’s intention-to-treat population, which included patients with HRD-positive and -negative tumors, the median PFS was 20.2 months (95% CI, 15.2-24.7) for rucaparib (n = 427) vs 9.2 months (95% CI, 8.3-12.2) for placebo (n = 111; (HR, 0.52; 95% CI, 0.40-0.68; log-rank P < .0001). In the HRD-negative population, the median PFS was 12.1 months (95% CI, 11.1-17.7) for rucaparib vs 9.1 months (95% CI, 4.0-12.2) for placebo (HR, 0.65; 95% CI, 0.45-0.95).

The phase 3 study enrolled patients with newly diagnosed, stage III to IV, advanced, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who experienced a response following frontline platinum-based chemotherapy and received cytoreductive surgery.1 Patients were also required to have an ECOG performance status of 0 or 1, and no prior frontline maintenance therapy was permitted.

In ATHENA-MONO, patients (n = 538) were randomly assigned in a 4:1 fashion to receive rucaparib at 600 mg twice per day or placebo. Treatment continued for up to 24 months, or until radiographic progression, unacceptable toxicity, or other reasons for discontinuation.

Stratification factors included HRD status, disease status after chemotherapy, and timing of surgery.

Baseline Characteristics and Safety for the HRD-Negative Subgroup

The median age was 64 years (range, 32-83) for the rucaparib arm vs 63 years (range, 31-80) for the placebo arm. The majority of patients in both groups were White (rucaparib, 80.4%; placebo, 81.6%), had an ECOG performance status of 0 (67.7%; 59.2%), had FIGO stage III disease (79.4%; 79.6%), had no disease burden (75.5%; 65.3%), had normal CA-125 levels (86.8%, 89.8%), underwent interval debulking (50.8%; 51.0%), had a complete R0 resection (63.5%; 61.2%), had no disease after surgery (54.5%; 49.0%), and had no residual disease after chemotherapy (75.7%; 75.5%).

Regarding safety in the HRD-negative population, treatment-emergent adverse effects (TEAEs) of any grade occurred in 96.8% of patients in the rucaparib arm vs 91.8% of those in the placebo arm. The rates of grade 3 or higher TEAEs were 58.2% and 26.5%, respectively.

The most common any-grade TEAEs included asthenia (rucaparib, 63.5%; placebo, 32.7%), nausea (59.3%; 32.7%), anemia (46.6%; 14.3%), increased alanine or aspartate aminotransferase levels (44.4%; 6.1%), dysgeusia (25.9%; 8.2%), neutropenia (25.9%; 2.0%), arthralgia (25.4%; 30.6%), abdominal pain (25.4%; 22.4%), diarrhea (23.8%; 26.5%), decreased appetite (22.8%; 16.3%), vomiting (22.8%; 6.1%), constipation (21.2%; 22.4%), thrombocytopenia (20.6%; 2.0%), and abdominal distension (11.6%; 20.4%).

Disclosures: Salutari reported serving on advisory boards for MSD, AbbVie, AstraZeneca, GSK, ImmunoGen, and Menarini; and serving as an invited speaker for MSD, AstraZeneca, GSK, and pharma&.

References

1. 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. Presented at: 2025 ESMO Gynecological Cancers Congress; June 19-21, 2025; Vienna, Austria. Abstract 75MO.
2. 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