As presented at the 2022 ASCO Annual Meeting (Abstract LBA5500) and simultaneously reported in the Journal of Clinical Oncology by Bradley J. Monk, MD, and colleagues, the phase III ATHENA-MONO trial found that maintenance rucaparib significantly improved progression-free survival vs placebo among patients with newly diagnosed advanced ovarian cancer, including those with homologous recombination deficiency (HRD)-positive disease.

Bradley J. Monk, MD

Study Details

The ongoing double-blind trial included 538 patients with stage III and IV high-grade disease from sites in 24 countries in Asia, Australia/New Zealand, Europe, and North America who had undergone surgical cytoreduction (R0 resection permitted) and responded to first-line platinum-doublet chemotherapy. Patients were randomly assigned 4:1 between October 2018 and September 2020 to receive rucaparib at 600 mg twice daily (n = 427) or placebo (n = 111) for up to 24 months. The primary endpoint was investigator-assessed progression-free survival, assessed first in the HRD-positive population (BRCA-mutant or BRCA wild-type/loss of heterozygosity–high tumor) and then in the intent-to-treat population.

Progression-Free Survival

Median follow-up was 26.1 months (95% confidence interval [CI] = 25.8–26.9 months) in the rucaparib group and 26.2 months (95% CI = 24.0–27.7 months) in the placebo group.

Among 185 vs 49 patients in the HRD-positive population, median progression-free survival was 28.7 months (95% CI = 23.0 months–not reached) with rucaparib vs 11.3 months (95% CI = 9.1–22.1 months) with placebo (hazard ratio [HR] = 0.47, 95% CI = 0.31–0.72, P = .0004). On blinded independent central review, median progression-free survival was not reached (95% CI = 28.7 months–not reached) vs 9.9 months (95% CI = 6.5 months–not reached; HR = 0.44, 95% CI = 0.28–0.70, P = .0004).

In the intent-to-treat population, median progression-free survival was 20.2 months (95% CI = 15.2–24.7 months) in the rucaparib group vs 9.2 months (95% CI = 8.3–12.2 months) in the placebo group (HR = 0.52, 95% CI = 0.40–0.68, P < .0001). Progression-free rates at 24 months were 45.1% vs 25.4%. On blinded independent central review, median progression-free survival was 25.9 months (95% CI = 16.8 months–not reached) vs 9.1 months (95% CI = 6.4–9.7 months; HR = 0.47, 95% CI = 0.36–0.63, P < .0001).

In the HRD-negative population, median progression-free survival was 12.1 months (95% CI = 11.1–17.7 months) vs 9.1 months (95% CI = 4.0–12.2 months; HR = 0.65, 95% CI = 0.45–0.95).

Adverse Events

Adverse events of any grade occurred in 96.7% of patients in the rucaparib group and 92.7% of the placebo group. Grade ≥ 3 adverse events occurred in 60.5% vs 22.7% of patients, with the most common in the rucaparib group being anemia (28.7%), neutropenia (14.6%), and increased transaminases (10.6%). In the rucaparib group, myelodysplastic syndrome was reported in one patient in the during treatment and acute myeloid leukemia was reported in one patient during long-term follow-up. Adverse events led to treatment discontinuation in 11.8% vs 5.5% of patients. No treatment-related deaths were reported.

The investigators concluded, “Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit vs placebo in patients with advanced ovarian cancer with and without HRD.”

Dr. Monk, of GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Phoenix, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Clovis Oncology Inc. For full disclosures of the study authors, visit ascopubs.org.