ATHENA (A Multicenter, Randomized, Double-Blind, Placebo- Controlled Phase 3 Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy)

Newly diagnosed stage III/IV ovarian cancer that responded to first-line platinum therapy

538

Maintenance

Double Blind, Randomized

ORR, PFS, OS, evaluated per RECIST

HRD status - FoundationOne CDx (BRCA MUT; BRCA WT/LOH high [LOH≥16%]; BRCA WT/LOH low [LOH<16%], BRCA WT/LOH indeterminate)

Ruc maint vs Placebo:

All patients (ITT):
ORR: 48.8 (n=427) vs 9.1% (n=111)
PFS: 20.2 vs 9.2 months, HR: 0.52 (0.40-0.68, p<0.0001)
TFST: 23.3 vs 12.1 months, HR: 0.52 (0.40-0.67)
PFS2: 36.0 vs 26.8 months, HR: 0.84 (0.63-1.13)
OS: NR vs 46.2 months, HR: 0.83 (0.58-1.17; 35% maturity)

HRD+ (incl. tBRCAMUT):
ORR: 58.5 (n=185) vs 10.0% (n=49)
PFS: 28.7 vs 11.3 months, HR: 0.47 (0.31-0.72, p=0.0004)
TFST: 32.7 vs 15.1 months, HR: 0.50 (0.33-0.76)
PFS2: NR vs 39.9 months, HR: 0.75 (0.46-1.24)
OS: NR vs NR, HR: 0.84 (0.44-1.58; 25% maturity)

Exploratory analyses:
BRCA MUT: PFS: NR vs 14.7 months, HR: 0.40 (0.21-0.75)
BRCA WT/LOH high: PFS: 20.3 vs 9.2 months, HR: 0.58 (0.33-1.01)
BRCA WT/LOH low: PFS: 12.1 vs 9.1 months, HR: 0.65 (0.45-0.95)
FIGO Stage III: PFS: 20.3 vs 10.4 months, HR: 0.64 (0.46-0.87, p=0.0048)
FIGO Stage IV: PFS: 17.5 vs 6.4 months, HR: 0.40 (0.25-0.64, p<0.0001)
Upfront surgery: PFS: 28.8 vs 18.4 months, HR: 0.64 (0.43-0.95, p=0.0302)
Interval surgery: PFS: 14.5 vs 8.3 months, HR: 0.44 (0.31-0.62, p<0.0001)
Residual disease after surgery: PFS: 12.2 vs 8.5 months, HR: 0.44 (0.27-0.73, p=0.0011)
No residual disease after surgery: PFS: 21.5 vs 10.4 months, HR: 0.59 (0.43-0.80, p=0.0006)
R0 after surgery, ITT: 25.1 vs 12.0 months, HR: 0.60 (0.43-0.84)
non-R0 after surgery, ITT: 13.9 vs 6.4 months, HR: 0.41 (0.27-0.62)
R0 after surgery, HRD+ (incl. tBRCA MUT): NR vs 22.1 months, HR: 0.52 (0.30-0.92)
non-R0 after surgery, HRD+ (incl. tBRCA MUT): 20.3 vs 9.1 monhts, HR: 0.29 (0.15-0.56)
PR after chemo, ITT: 12.2 vs 6.4 months, HR: 0.37 (0.21-0.65)
CR after chemo, ITT: 15.6 vs 6.4 months, HR: 0.48 (0.23-1.03)
PR after chemo, HRD+ (incl. tBRCA MUT): 14.8 vs 9.1 months, HR: 0.43 (0.18-1.02)
CR after chemo, HRD+ (incl. tBRCA MUT): 25.8 vs NR, HR: 0.41 (0.10-1.63)

Ruc vs Placebo:
Serious AE: 1 MDS, 1 AML in Ruc arm (0.5%)
Grade 3-4 AE: overall (60.5 vs 22.7%), anemia (28.7 vs 0%), neutropenia (14.6 vs 0.9%)

Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD

Monk BJ et al. ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer. J Clin Oncol 40, 2022; suppl 17; abstr LBA5500
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA5500

Monk BJ et al. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol (2022) 40(34):3952-3964
https://pubmed.ncbi.nlm.nih.gov/35658487/

Kristeleit R et al. Interim Post-Progression Data and Updated Survival in Patients With Newly Diagnosed Advanced Ovarian Cancer in ATHENA-MONO. SGO 2024 Scientific Plenary II
https://www.clearityfoundation.org/wp-content/uploads/2024/05/Kristeleit-R-et-al.-ATHENA-Mono-abstract-SGO-2024.pdf