Maintenance rucaparib improves PFS compared to placebo in ovarian cancer with or without high risk of progression
Patients with newly diagnosed ovarian cancer with or without high risk of progression experienced a progression-free survival benefit with rucaparib maintenance therapy compared to placebo, regardless of molecular characteristics .
A progression-free survival (PFS) advantage was observed after maintenance treatment with rucaparib (Rubraca) compared to placebo in all subgroups of patients with newly diagnosed ovarian cancer, based on the results of the phase 3 ATHENA-MONO study (NCT03522246).
The results of the study, which were presented at the 2022 European Society for Medical Oncology, reported that in patients with R0 surgical resection and homologous recombination deficiency (HRD), median PFS was not achieved (NR; 95% CI, 28.7-NR) after treatment with rucaparib versus 22.1 months (95% CI, 9.2-NR; RR, 0.52; 95% CI, 0.30-0.92); in the intent-to-treat (ITT) population, the median PFS was 25.1 months (95% CI, 18.6-31.3) and 12.0 (95% CI, 9.1-20 .1), respectively (HR, 0.60; 95% CI, 0.43-0.84).
Among patients who did not undergo R0 resection and who were HRD positive, the median PFS was 20.3 months (95% CI, 13.9-25.8) and 9.1 months (CI 95%, 3.5-9.2; HR, 0.29; 95% CI, 0.15-0.56) among those treated with rucaparib and placebo, respectively. Additionally, in the ITT group, the median PFS was 13.9 months (95% CI, 10.3-17.8) and 6.4 months (95% CI, 3.7-9.2 ), respectively (HR, 0.41; 95% CI, 0.27-0.62).
PFS was also assessed in terms of response to first-line chemotherapy. Among patients who achieved a partial response (PR), the median PFS was 14.8 months (95% CI, 9.1-25.6) and 9.1 months (95% CI, 3.5 -9.2; HR, 0.43; 95% CI, 0.18-1.02) in the HRD population and 12.2 months (95% CI, 9.2-19.7) and 6. 4 months (95% CI, 3.7-9.2) in the ITT population after treatment with rucaparib and placebo, respectively. Among complete responders (CR), the median PFS was 25.8 months (95% CI, 17.4-NR) and NR (95% CI, 2.5-NR) in the HRD population after treatment by rucaparib and placebo, respectively. In the ITT population, the median PFS was 15.6 months (95% CI, 10.2-25.8) and 6.4 months (95% CI, 2.7-NR; HR, 0. 48; 95% CI, 0.23-1.03), respectively. Safety was similar across patient subgroups.
The objective of the ATHENA-MONO trial was for investigators to assess the PFS of rucaparib and placebo in subgroups of patients with newly diagnosed ovarian cancer, including surgical outcomes by assessment of the surgeon and by the response to first-line chemotherapy by radiographic examinations.
To be eligible for the study, patients had to have newly diagnosed high-grade disease and a FIGO stage of III to IV. Patients were required to have completed treatment with 4 to 8 cycles of doublet platinum-based chemotherapy and first-line surgery. After primary treatment, patients were required to have achieved CR or PR, as well as cytoreductive surgery. Stratification factors included HRD status, disease status after chemotherapy, and timing of surgery. Patients were randomized 4:1 to receive treatment with rucaparib 600 mg (n=427) or placebo (n=111) twice daily orally for 24 months or until radiographic progression, unacceptable toxicity, or another reason for stopping.
Kristeleit R, Ghamande S, Lim M, et al. Rucaparib Maintenance Treatment in Patients (pts) with Newly Diagnosed Ovarian Cancer (OC): Definition of Benefit by Disease Risk Subgroups in the Phase 3 Study ATHENA-MONO. Anne Oncol. 2022;33(supplement 7):527MB. doi:10.1016/announce/announce1054