Abstract
We report the long-term efficacy and safety from the multicenter, randomized, double-blind, placebo-controlled, phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 (NCT03522246) study of first-line rucaparib maintenance for advanced ovarian cancer.
Patients were randomized 4 : 1 to oral rucaparib + intravenous (i.v.) placebo or oral + i.v. placebo. Stratification factors were homologous recombination deficiency (HRD; BRCA mutation and loss of heterozygosity status) classification, residual disease post-chemotherapy, and surgical timing. The primary endpoint was investigator-assessed progression-free survival (invPFS) in HRD and intent-to-treat (ITT) populations. Overall survival (OS) and safety were secondary endpoints. Second event of progression (PFS2) and time to first subsequent treatment (TFST) were exploratory. Interim OS and final safety analyses data cut-off was 9 March 2023. Updated invPFS, PFS2, and TFST analyses data cut-off was 5 May 2025.
Median invPFS follow-up was ∼59 months for both rucaparib (HRD, n = 185; ITT, n = 427) and placebo (HRD, n = 49; ITT, n = 111). invPFS was significantly longer with rucaparib versus placebo in the HRD [31.4 versus 12.0 months; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.35-0.76] and ITT (20.2 versus 9.2 months; HR 0.53, 95% CI 0.42-0.69) populations. Interim OS was immature (OS maturity: ITT 35%) with the median (95% CI) OS not reached with rucaparib and 46.2 (34.6-not reached) months with placebo for the ITT population (HR 0.83, 95% CI 0.58-1.17). ITT TFST (median 23.6 versus 12.1 months) and PFS2 (35.1 versus 26.9 months) were longer with rucaparib versus placebo. Overall, 34.6% of patients receiving rucaparib completed the 24-month treatment cap versus 17.3% receiving placebo. As of 5 May 2025, 40.0% of patients on rucaparib were still on study and in long-term follow-up. Safety remained consistent with the primary analysis.
Rucaparib monotherapy provides significant and durable long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD.