First-line rucaparib maintenance therapy provides long-term benefit in newly diagnosed ovarian cancer

In addition to providing a progression-free survival (PFS) advantage compared with placebo, maintenance therapy with rucaparib also prolonged time to first subsequent treatment (TFST) and time to second disease progression or death (PFS2) in patients with newly diagnosed ovarian cancer.

In 2024, overseas released the latest results of the long-term analysis of the ATHENA-MONO part of the Phase 3 ATHENA study (NCT 03522246). In the intention-to-treat (ITT) population, patients who received rucaparib (n=427) had a median TFST of 23.3 months (95% CI, 19.3-26.8) compared with those who received placebo. The median follow-up for treated patients was 12.1 months (95% CI, 10.1-16.1) after 37.1 months (n = 111; HR, 0.52; 95% CI, 0.40-0.67). Median PFS2 was 36.0 months (95% CI, 29.5-44.6) and 26.8 months (95% CI, 21.7 not reached [NR]) for rucapanib and placebo, respectively (HR, 0.84; 95% CI, 0.63-1.13).

In theHRD population, the median TFST was 32.7 months (95% CI, 26.0-NR) in the rucaparib group (n=185) and 15.1 months (95% CI, 10.3-13.7) in the placebo group (n=49; HR, 0.50; 95% CI, 0.33-0.76). Median PFS2 was NR (95% CI, 39.0 to NR) in the rucaparib arm and 39.9 months (95% CI, 24.2 to NR) in the placebo arm (HR, 0.75; 95% CI, 0.46 to 1.24). At the time of this analysis, overall survival (OS) data were immature. The ATHENA-MONO study results support the European Commission's approval of rucaparib as a first-line treatment for patients with advanced ovarian cancer.

The long-term endpoints of the ATHENA-MONO study strengthen the use of rucaparib in the first-line (maintenance) setting as an add-on agent whose effects are independent of molecular status and whose toxicity is very manageable.

InATHENA-MONO trial, what is the rationale for assessing the efficacy of first-line rucaparib maintenance therapy according to HRD or BRCA status?

Among women with advanced ovarian cancer who achieve a complete or partial response after first-line treatment combined with surgery and chemotherapy, maintenance therapy is associated with better survival outcomes. Previous data suggest that these survival outcomes vary by molecular status. We've seen otherPARP inhibitors are used for first-line treatment, while rucapanib is also used for relapse treatment. The purpose of the ATHENA-MONO study is to determine whether women with advanced ovarian cancer (who experience a complete or partial response) treated with surgery and chemotherapy would benefit from [first-line] rucaparib maintenance [treatment] for up to 2 years. Long-term follow-up analysis examined TFST, PFS2, and OS. This is an ad hoc analysis conducted primarily to support the application to the European Medicines Agency for rucaparib for first-line treatment.

Key efficacy findings from this 3-year follow-up study of patients in the ATHENA-MONO study demonstrate the clinical benefit of rucaparib beyond first progression and 2-year treatment completion. Prolongation of TFST and PFS2 (first-line rucaparib maintenance therapy) was observed compared with placebo. Giving rucaparib in the first-line setting essentially allows women to maintain benefit through and follow their second-line treatment. This is an important and reassuring finding.

Additionally, the operating system data in the report is immature. It has matured by 35% in theITT population and by 25% in the HRD population. However, a trend toward improved operating systems was observed. The hazard ratio was less than 1 in both main analysis populations. Although neither the rucapanib nor placebo arms in the HRD group reached median OS, the placebo group in the ITT population did. For OS, separation of the curves occurs at approximately 30 months.

Rucaparib has been studied quite intensively as maintenance therapy in the setting of relapse. No new signals were seen for the use of rucaparib in the first-line setting compared with the safety findings in the relapse setting. As with all PARP inhibitors, some patients developed myelodysplastic syndromes and acute myeloid leukemia, but the incidence of these malignancies did not appear to be significantly different compared with placebo. The toxicity profile is very easy to control.