49MO Updated progression-free survival (PFS) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) treated with rucaparib (RUC) in ATHENA-MONO

RUC provided a sustained PFS benefit in pts with newly diagnosed advanced OC after first-line (1L) treatment in the ATHENA-MONO study (NCT03522246). We report updated PFS analyses (data cutoff 01 March 2024). Pts with high-grade, FIGO stage III-IV OC with response to 1L treatment were randomized 4:1 to treatment with 600 mg BID RUC (N = 427) or placebo (PBO, N = 111) for up to 2 y. An exploratory analysis was done to evaluate updated investigator-assessed PFS (INV). It included the primary populations (homologous recombination deficiency [HRD] and intent to treat [ITT]), non-nested HRD subgroups, and low/high-risk pts according to FIGO stage/surgical outcome and surgery timing. For pts in complete response (CR) at baseline, recurrence-free survival was defined as time from randomization to disease recurrence (new lesions by imaging) or death. After a median of 4.0 and 3.5 y of follow-up, an additional 1.9 and 1.6 y of follow-up, respectively, median PFS was consistently longer or not reached (NR) in pts treated with RUC than with PBO in ITT populations as well as in the HRD subgroup and the non-nested HRD subgroups (Table). In the higher-risk subgroup 27.7% of RUC vs 8.6% of PBO-arm pts were progression-free at 4 y; in the lower-risk subgroup 41.9% vs 37.2% of pts, respectively, were progression free at this time point. Among pts in CR at baseline, risk of disease recurrence or death was reduced by 51%. The safety profile of RUC was consistent with that from the primary endpoint analysis (23 March 2022). Three new cases of myelodysplastic syndrome or acute myeloid leukemia were reported since the primary analysis; the incidence was the same in the RUC and PBO arms (<1%).Table: 49MORUC vs PBO23 Mar 20221 Mar 2024Blinded independent central reviewINVINVMedian PFS, mo, HR (95% CI)Overall25.9 vs 9.1 0.47 (0.36-0.63)20.2 vs 9.2 0.52 (0.40-0.68)20.2 vs 9.2 0.53 (0.41-0.68)HRDNR vs 9.9 0.44 (0.28-0.70)28.7 vs 11.3 0.47 (0.31-0.72)31.4 vs 12.0 0.49 (0.33-0.73)BRCANR vs NR 0.48 (0.23-1.00)NR vs 14.7 0.40 (0.21-0.75)NR vs 16.7 0.47 (0.26-0.84)Non-BRCA LOHhigh27.8 vs 9.1 0.46 (0.26-0.81)20.3 vs 9.2 0.58 (0.33-1.01)22.3 vs 9.2 0.56 (0.33-0.92)Non-BRCA LOHlow12.0 vs 6.4 0.60 (0.40-0.89)12.1 vs 9.1 0.65 (0.45-0.95)12.1 vs 9.1 0.66 (0.46-0.96)Non-BRCAunknown17.4 vs 6.5 0.33 (0.16-0.68)17.5 vs 8.9 0.39 (0.20-0.78)17.5 vs 8.9 0.38 (0.19-0.76)LOH, loss of heterozygosity. Open table in a new tab LOH, loss of heterozygosity. RUC maintained a clinically significant improvement in PFS with 4.0 y of follow-up in pts with newly diagnosed advanced OC in pts with both low and high risk of progression. No new safety signals were identified.