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.