For patients with advanced ovarian cancer, first-line maintenance therapy with rucaparib delays the need for first and second subsequent therapies by roughly a year at each step, according to new data from the phase 3 ATHENA-MONO trial.

Among patients randomized to rucaparib after surgery and standard chemotherapy, the median time to first subsequent therapy was just under 24 months vs 12 months among patients randomized to placebo. The median time to second subsequent therapy was 38 months in the rucaparib group and 27.5 months in the placebo group.

Experts said the findings, presented at the ESMO Gynecological (ESMO Gyn) Cancers Congress 2026 in Copenhagen, Denmark, bolster the role of rucaparib and other PARP inhibitors in first-line maintenance therapy for patients with advanced ovarian cancer.

Delaying subsequent therapies can have a meaningful impact on patients’ quality of life, investigator Emily Prendergast, MD, of Cedars-Sinai Medical Center in Los Angeles, noted in an interview with Medscape Medical News.

“Rucaparib provides benefit even beyond the 2 years of [treatment] received during the ATHENA-MONO trial,” she said.

The ATHENA-MONO trial enrolled patients with newly diagnosed stage III-IV high-grade ovarian cancer who underwent cytoreductive surgery and had a complete or partial response to first-line platinum-doublet chemotherapy. Patients were randomized 4:1 to oral rucaparib monotherapy 600 mg twice daily or placebo for up to 24 months.

Prior results have shown that rucaparib has a durable benefit in terms of progression-free survival. At 5 years, progression-free survival was 29% in the intervention arm vs 16% in the placebo arm. Overall survival data remain immature.

While overall survival is the gold-standard endpoint, Prendergast said, it’s also an outcome that can be difficult to interpret in this setting: Patients who progress frequently cross over to active treatment, often including PARP inhibitors, and many live for years through several additional lines of therapy. 

“There was no protocol-mandated crossover in ATHENA-MONO, but in real-life terms, many placebo-arm patients went on to receive a PARP inhibitor in a subsequent line,” Prendergast told Medscape Medical News. 

Time to first and second subsequent therapies were exploratory endpoints in the trial. And they offer additional insights beyond progression-free survival, which also has its limitations as an endpoint, Prendergast noted.

“In a maintenance trial,” she said, “progression-free survival can be inflated by assessment artifacts — scan intervals, variability in how reads are interpreted, censoring when a patient drops out. And it stops the clock at first progression.”

Time to subsequent therapies, Prendergast said, marks when a patient actually needs the next line of treatment, and the one after that, based on clinical assessment.

Overall, her team found that most trial patients had received at least one subsequent anticancer therapy by the 5-year data cutoff, although the proportion was smaller in the rucaparib arm: 63% of 427 patients in the rucaparib arm had received subsequent therapy vs 78% among 111 patients in the placebo arm.

More patients progressed to second line or beyond in the placebo arm than in the rucaparib arm (52% vs 40%), whereas more patients in the rucaparib arm remained in long-term follow-up without any subsequent therapy compared with the placebo arm (26% vs 14%).

“This points to more durable remissions in the patients who received rucaparib maintenance in the first-line setting,” Prendergast told Medscape Medical News. “It could reflect a subset achieving cure.”

However, that will remain unclear until overall survival data are mature, she stressed.

As for types of therapy, platinum-based chemotherapy was used as the first subsequent therapy for 79% of rucaparib-arm patients and 70% of placebo-arm patients; a PARP inhibitor was incorporated in 14% vs 32%, respectively. That pattern was partly reversed at second subsequent therapy, where platinum use was lower in rucaparib-arm patients than in placebo-arm patients (38% vs 53%); PARP inhibitor use remained lower (6% vs 14%).

Overall survival “is the goal we want to reach,” said study discussant Frederik Marmé, MD, PhD, a gynecologic oncologist at University Hospital Mannheim and the Medical Faculty Mannheim of Heidelberg University in Mannheim, Germany.

But he agreed that intermediate, “patient-centered” outcomes, including time to subsequent therapies, offer valuable information.

These new data, Marmé said, “strongly support” the use of PARP inhibitors in first-line maintenance, noting that the benefit with rucaparib held even though a substantial proportion of patients in the placebo arm later received a PARP inhibitor. 

Marmé pointed out, however, that the study does not provide information according to homologous recombination deficiency (HRD) status. That leaves the question of whether the delay in subsequent therapies is driven by patients with HRD-positive disease.

For now, Prendergast said the data give clinicians additional information to discuss with patients: PARP inhibitor maintenance may give them more time to “live their lives” without dealing with subsequent therapies and their side effects.

ATHENA-MONO was funded by Clovis Oncology and pharma& GmbH. Prendergast reported financial relationships with AstraZeneca. Marmé reported financial relationships with numerous companies, including Clovis Oncology, Roche/Genentech, Novartis, and Pfizer.