First-Line Maintenance Rucaparib Achieves Longer PFS Vs Placebo Across Subgroups in Newly Diagnosed Ovarian Cancer


Results from the phase 3 ATHENA-MONO study suggest that rucaparib could serve as a promising first-line maintenance treatment option in newly diagnosed ovarian cancer.

First-line maintenance rucaparib (Rubraca) yielded higher progression-free survival (PFS) compared with placebo among patients with newly diagnosed ovarian cancer regardless of cytoreductive surgery outcome and was favored across all subgroups, according to the results of the phase 3 ATHENA-MONO study (GOG-303/ENGOT-ov45; NCT03522246), which were presented during the 2022 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS).

In the trial’s intent-to-treat (ITT) and homologous recombination deficiency (HRD) populations, rucaparib produced longer PFS than placebo in both groups, including in patients who received R0 and non-R0 cytoreductive surgery.

When PFS was assessed by chemotherapy response in the HRD group, the median PFS was 14.8 months (95% CI, 9.1-25.6) with rucaparib vs. 9.1 months (95% CI, 3.5-9.2) with placebo in those who experienced a partial response (PR; hazard ratio [HR], 0.43; 95% CI, 0.18-1.02). Moreover, in complete responders (CRs) within the HRD group, the median PFS was 25.8 months (95% CI, 17.4-not reached [NR]) in the rucaparib arm vs NR in the placebo arm (95% CI, 2.5-NR). In the ITT population who experienced PRs following chemotherapy, the median PFS was 12.2 months (95% CI, 9.2-19.7) with rucaparib maintenance and 6.4 months (95% CI, 3.7-9.2) with placebo (HR, 0.37; 95% CI, 0.21-0.65). Among those who experienced CRs, the median PFS was 15.6 months (95% CI, 10.2-25.8) in the rucaparib arm vs 6.4 months (95% CI, 2.7-NR) in the placebo arm (HR, 0.48; 95% CI, 0.23-1.03).

Investigators also assessed PFS by cytoreductive surgical outcomes and responses to first-line chemotherapy. Among those in the HRD group who had an R0 cytoreduction surgery, the median PFS was NR (95% CI, 28.7-NR) in the rucaparib arm vs 22.1 months in the placebo arm (95% CI, 9.2-NR; HR, 0.52; 95% CI, 0.30-0.92). Additionally, the median PFS among those with a non-R0 resection was 20.3 months (95% CI, 13.9-25.8) and 9.1 months, respectively (95% CI, 3.5-9.2; HR, 0.29; 95% CI, 0.15-0.56). Among those in the ITT population who had an R0 cytoreductive surgery, the median PFS was 25.1 months (95% CI, 18.6-31.3) in the rucaparib arm vs 12.0 months (95% CI, 9.1-20.1) in the placebo arm (HR, 0.60; 95% CI, 0.43-0.84). In the non-R0 population, the median PFS was 13.9 months (95% CI, 10.3-17.8) vs 6.4 months (95% CI, 3.7-9.2), respectively (HR, 0.41; 95% CI, 0.27-0.62).

Following cytoreductive surgery and chemotherapy, patients were randomly assigned 4:1 to receive either 600 mg of rucaparib twice daily (n = 427) or a matched placebo (n = 111), both taken twice a day orally. Treatment continued for 24 months, or until radiographic progression or unacceptable toxicity. Patients were eligible to participate in the trial if they had newly diagnosed stage III or IV high-grade ovarian cancer and had completed 4 to 8 cycles of frontline platinum-doublet chemotherapy and surgery. To be included in the analysis, patients needed to achieve a CR or PR following chemotherapy and surgery and received primary or interval cytoreductive surgery.

Patients in the ITT and HRD populations were divided into subcategories based on baseline factors. In the ITT population, 62.5% of patients had an R0 surgery and 37.5% had a non-R0 surgery. A total of 18.2% of patients achieved a PR and 5.6% had a CR following first-line chemotherapy. In the HRD population, 59.8% had an R0 resection and 40.2% had a non-R0 cytoreductive surgery. Moreover, 17.9% of patients in the HRD population experienced a PR and 17.9% had CRs.

In the ITT PFS subgroup analysis, patients with stage III ovarian cancer had a median PFS of 20.3 months with rucaparib vs. 10.4 months with placebo (HR, 0.64; 95% CI, 0.46-0.67). Moreover, the median PFS for patients with stage IV disease was 17.5 months with rucaparib compared with 6.4 months with placebo (HR, 0.40; 95% CI, 0.25-0.64). The median PFS for patients who underwent primary surgery was 28.8 months vs 18.4 months, respectively (HR, 0.64; 95% CI, 0.43-0.95). Additionally, for those who received interval debulking, the median PFS was 14.5 months vs 8.3 months, respectively.

Overall, safety data were balanced across subgroups. Discontinuations of maintenance rucaparib due to treatment-emergent adverse effects (TEAEs) were twice as frequent among patients with an R0 surgical outcome or no evidence of disease on screening scan vs patients with a non-R0 surgical outcome or who have residual disease on screening scans. Overall, these safety data indicated that patients with no disease were more likely to discontinue study treatment. The median treatment duration for those with an R0 surgical outcome was 15.7 months in the rucaparib arm vs 12.2 months among those with a non-R0 surgical outcome. Additionally, the median treatment duration was 15.2 months for those with no evidence of disease vs 12.8 months for those with evidence of residual disease.


O’Malley D, Christopoulou A, Lim MC, et al. Efficacy analysis by disease risk subgroup for the phase 3 ATHENA-mono study (GOG-3020/ENGOT-ov45) evaluating rucaparib maintenance treatment in patients with newly diagnosed ovarian cancer. Presented at: 2022 International Gynecologic Cancer Society Annual Meeting; September 29-October 1, 2022; New York, NY. Abstract O026. Accessed September 30, 2022.

Related Videos
Considering cystectomy in patients with bladder cancer may help with managing the shortage of Bacillus Calmette-Guerin, according to Joshua J. Meeks, MD, PhD, BS.
Anemia in patients who receive talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer appears to be manageable without any compromises in patient-reported outcomes and quality of life.
Patients with locally advanced or metastatic urothelial cancer and visceral disease may particularly benefit from enfortumab vedotin plus pembrolizumab, according to Amanda Nizam, MD.
High-grade adverse effects with zanidatamab plus palbociclib and fulvestrant seem to be uncommon in patients with HER2-positive, hormone receptor–positive, metastatic breast cancer, according to Sara Hurvitz, MD, FACP.
Black male patients with breast cancer appear to experience worse survival outcomes compared with White patients when controlling for clinicopathological variables, according to Jason (Jincong) Q. Freeman, MPH, MS.
Results from the ECOG-ACRIN E4112 trial appear to support the use of DCIS scores for identifying patients with breast cancer who may be eligible to omit radiotherapy following MRI-guided surgery.
Providers should inform patients with breast cancer that selecting later-line therapies following prior treatment with CDK4/6 inhibitors is a “developing area,” says Abigail M. Johnston, JD.
Data from the phase 3 NATALEE trial highlight a positive toxicity profile for ribociclib as an adjuvant therapy for patients with hormone receptor–positive, HER2-negative breast cancer, says Neil M. Iyengar, MD.
Future research will focus on ctDNA dynamics change over time in the full translational cohort of patients with hormone receptor–positive breast cancer in the phase 3 monarchE study, says Stephanie L. Graff, MD.
Findings from a National Cancer Database analysis highlight no statistically significant differences in survival outcomes with chemotherapy for patients over 81 years old with triple-negative breast cancer compared with those who do not receive chemotherapy.
Related Content