Rubraca Maintenance Therapy Delays Progression for Patients With Advanced Ovarian Cancer

New 5-year data from the phase 3 ATHENA-MONO trial, published in Annals of Oncology, show that maintenance treatment with Rubraca (rucaparib), a type of targeted therapy known as a PARP inhibitor that works by blocking cancer cells’ ability to repair their DNA, significantly extended the time patients with newly diagnosed advanced ovarian cancer lived without their disease worsening compared with placebo. The international study evaluated Rubraca as a follow-up treatment after patients responded to platinum-based chemotherapy, aiming to determine whether continuing therapy could help keep the cancer under control longer. Results suggest that for some patients, this approach led to several additional years without disease progression.

What longer “Progression-free survival” means for patients

After finishing chemotherapy, many patients ask the same question: how long will the cancer stay away?

The main goal of the ATHENA-MONO trial was to measure progression-free survival. This refers to how long patients live without their cancer growing or returning. For patients, this can mean more time feeling stable, fewer immediate treatment changes and potentially more time before symptoms return.

In patients whose tumors were HRD-positive, those who received Rubraca went a median of 31.4 months before their cancer worsened. In comparison, those who received placebo went 12 months before progression. In simple terms, that is more than 2 1/2 years versus about 1 year.

The hazard ratio was 0.52, meaning there was a 48% reduction in the risk of the cancer worsening or death during the study period.

When looking at all patients in the trial, regardless of HRD status, the median time without progression was 20.2 months with Rubraca compared with 9.2 months with placebo. This represents a 47% reduction in the risk of progression or death.

For many patients, what matters most is the long-term picture. At 5 years, 29% of patients taking Rubraca had not experienced disease progression, compared with 16% of patients taking placebo. Among those who had a complete response after chemotherapy, 25% of patients in the Rubraca group were still progression free at 5 years.

While not every patient will experience long-term benefit, these results suggest that a meaningful portion of patients may gain several additional years before their cancer worsens.

Overall survival data are still early, with 35% maturity. Although results trend in favor of Rubraca, it is too soon to know whether patients live longer overall.

Who participated in the study?

ATHENA-MONO was an international, randomized, double-blind, placebo-controlled, phase III trial, meaning patients from multiple countries were randomly assigned to receive either Rubraca or a placebo, and neither the patients nor their doctors knew which treatment was being given. This type of study design helps ensure the results are as fair and unbiased as possible when comparing how well a treatment works and how safe it is.

The study included adults with newly diagnosed stage 3 or 4 high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer whose disease had responded to platinum doublet chemotherapy. Patients needed to be well enough to carry out daily activities with minimal limitations and have adequate organ function.

Between October 2018 and September 2020, 427 patients were assigned to receive Rubraca and 111 were assigned to placebo.

Patients took Rubraca as an oral tablet at a dose of 600 mg twice daily. Treatment could continue for up to 24 months, or until the cancer progressed or side effects became too difficult to manage.

Maintenance therapy is designed to help keep cancer controlled after chemotherapy has worked. For patients, this approach aims to extend the period of remission.

What patients should know about side effects

Like most cancer treatments, Rubraca was associated with side effects.

Nearly all patients in both groups experienced at least one side effect of any severity: 96.5% in the Rubraca group and 92.7% in the placebo group.

More serious side effects occurred in 60.5% of patients taking Rubraca compared with 23.6% of those taking placebo. These side effects sometimes required dose adjustments or temporary treatment pauses. Treatment was interrupted because of side effects in 60.7% of patients receiving Rubraca and permanently stopped in 11.8%.

The most common side effects included nausea in 56.9% of patients, fatigue in 55.8%, anemia in 46.6% and elevated liver enzymes in 42.8%. These are typically monitored with regular lab work and clinic visits.

A small percentage of patients developed myelodysplastic syndrome or acute myeloid leukemia: 1.4% in the Rubraca group and 0.9% in the placebo group.

Importantly, no new safety concerns were identified with longer follow-up.

For patients considering maintenance therapy, the decision often involves weighing the possibility of delaying cancer recurrence against the risk of side effects and the commitment to taking daily medication for up to 2 years. These findings provide data that patients can use in conversations with their oncology team when deciding whether maintenance treatment is right for them.

References

1. “Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study” by Dr. Rebecca S. Kristeleit, et al., Annals of Oncology.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.