First-line rucaparib maintenance treatment is effective and yields significant benefit in patients with ovarian cancer who responded to platinum-based chemotherapy, according to results from the ATHENA-MONO trial presented at the 2022 ASCO Annual Meeting.

“While PARP inhibitors have shown efficacy as first-line maintenance treatment for patients with ovarian cancer, questions remain about the patient population that may benefit from their use,” wrote Bradley J. Monk, MD, FACS, FACOG, GOG Foundation, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, et al, who conducted the phase 3, double-blind, ATHENA trial.

The ATHENA study was designed to evaluate the efficacy of rucaparib as first-line maintenance therapy in a broad cohort that included those without BRCA mutations, evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics. The primary end point of the trial was investigator-assessed progression-free survival (PFS) assessed in a step-down procedure first in the HRD population and then in the intent-to-treat (ITT) population.

As of the cutoff date of March 23, 2022, a total of 538 patients with stage III-IV high-grade ovarian cancer who underwent cytoreductive surgery (R0 permitted) and responded to 4 to 8 cycles of first-line platinum-doublet (bevacizumab allowed with chemotherapy) treatment were included in the study. These patients were randomized based on HRD status, residual disease status after chemotherapy, and timing of surgery in a 4:1 ratio to receive oral rucaparib 600 mg twice daily (n = 427) or placebo (n = 111; median time on treatment, 14.7 and 9.9 months, respectively).

Among patients with HRD, the median PFS was observed to be 28.7 months with rucaparib versus 11.3 months with placebo (P = .0004); those in the ITT population had a PFS of 20.2 months and 9.2 months, respectively (P <.0001).

The most frequently reported grade ≥3 treatment-emergent adverse events were anemia (rucaparib, 28.7% vs placebo, 0%), neutropenia (14.6% vs 0.9%, respectively), and increased alanine aminotransferase and aspartate aminotransferase (10.6% vs 0.9%, respectively).

Treatment doses with rucaparib were reduced, interrupted, or discontinued among 49.4%, 60.7%, and 11.8% of patients with these adverse events.

“Rucaparib monotherapy is effective as first-line maintenance with significant benefit versus placebo observed in the ITT and HRD populations, as well as the non-nested subgroup of patients without known HRD,” Dr Monk and colleagues concluded.

Source:

Monk BJ, Parkinson C, Lim MC, 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. Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract LBA5500.