After Considering Patients’ Well-being, Rubraca Continues to Benefit Women with Recurrent Ovarian Cancer, Analysis Shows

Maintenance therapy with Rubraca (rucaparib) tablets continues to benefit women with recurrent ovarian cancer after weighing in patients’ perceptions about their health, disease symptoms, and treatment toxicity, a retrospective analysis of Clovis Oncology‘s ARIEL3 Phase 3 clinical trial found.

The data were presented recently at the International Society for Pharmacoeconomics and Outcomes (ISPOR) 2019 Meeting in New Orleans, Louisiana, in the poster “Patient-Centered Outcomes in ARIEL3, a Phase 3, Randomized, Placebo-Controlled Study of Rucaparib Maintenance Treatment in Patients with Recurrent Ovarian Carcinoma.”

ARIEL3 is a Phase 3 clinical trial (NCT01968213) showing that maintenance with Rubraca extended the time women lived without disease worsening from 5.4 months to 10.8 months, representing a 64% reduction in the risk of disease progression or death.

The trial enrolled 564 women with high-grade, recurrent ovarian carcinoma, who had responded to platinum-based chemotherapy but whose cancer came back. Of these patients, 375 were assigned Rubraca, given as 600 mg tablets twice daily, and 189 were assigned a placebo, in 28-day treatment cycles.

While Rubraca worked better in patients with BRCA-mutated cancers (delaying disease progression or death from 5.4 months to 16.6 months), or for cancers with other mutations involved in DNA repair (from 5.4 months to 13.6 months), the medicine continued to delay disease progression in the overall population.

The poster presented recently at the ISPOR meeting highlights a retrospective (post-hoc) analysis of the trial data, re-assessing outcomes in a more patient-centered manner, incorporating patients’ perceptions about their own well-being.

During the study, patients were asked to complete EQ-5D-3L, a patient survey for health-related quality of life, at four intervals: screening; on day one of each treatment cycle; at treatment discontinuation; and at the 28-day follow-up visit.

In their re-analysis, researchers used this data to weigh the main study goal — time to disease worsening or death, or progression-free survival (PFS) — with EQ-5D-3L scores. So, this derived measure, termed quality-adjusted PFS (QA-PFS), represents the PFS adjusted for how much patients rated their health status.

Likewise, quality-adjusted time without symptoms or toxicity (Q-TWiST) was calculated by subtracting all the time patients experienced treatment toxicity or disease symptoms from their survival data, and then multiplying it by a patient-derived utility value extracted from EQ-5D scores. According to Clovis Oncology, this reflects patients’ perceptions of the impact of toxicity on survival.

The analysis basically showed that Rubraca continued to benefit patients when using these patient-centered outcomes.

In the overall population, quality-adjusted survival without disease worsening (QA-PFS) remained significantly longer for women who received Rubraca, compared with placebo (mean 12.0 vs. 5.7 months) and even more in patients with a BRCA mutation (15.3 vs. 5.9 months).

The mean time patients spent without disease symptoms or toxic effects (severe or worse) (Q-TWiST) also was significantly longer in the Rubraca group compared with placebo, both in the overall population (13.3 vs 6.4 months) and in patients with a BRCA mutation (16.4 vs 6.7 months).

“It is very important to evaluate patients’ perceptions of their well-being during any type of treatment, particularly in the maintenance therapy setting in which patients may be on therapy for an extended period of time,” Jonathan Ledermann, MD, professor at UCL Cancer Institute and UCL Hospitals, London, said in a press release.

“These QA-PFS and Q-TWiST data from ARIEL3 integrate the patient perspective over the course of follow-up until progression to reflect their overall experience over time and suggests that the toxicity which may occur with rucaparib doesn’t outweigh its clinical benefit as maintenance treatment for women with recurrent ovarian cancer,” he said.