Rubraca Extends Time to Disease Progression in Recurrent OC, Regardless of Chemo Response, Analysis Shows

Maintenance treatment with Clovis Oncology’s Rubraca (rucaparib) extends the time until disease progression in women with recurrent ovarian cancer, exploratory analysis from a Phase 3 trial shows.

This occurs regardless of the patients’ response to prior treatment with platinum-based chemotherapy agents.

The analysis will be presented at the European Society for Medical Oncology (ESMO) Congress 2019, being held Sept. 27 to Oct. 1 in Barcelona, Spain. Jonathan Ledermann, professor at the University College of London (UCL) Cancer Institute, will present the trial’s findings in a poster titled, “Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the Phase 3 study ARIEL3 of rucaparib maintenance treatment.”

Rubraca is a PARP inhibitor that works by blocking the activity of PARP enzymes. These enzymes are involved in DNA repair, and in the control of programmed cell death. By blocking the activity of these enzymes, Rubraca prevents cancer cells from repairing their DNA, eventually eliminating them.

The U.S. Food and Drug Administration (FDA) approved Rubraca in 2016 for the treatment of women with advanced forms of ovarian cancer. Last year, based on findings from ARIEL 3, the FDA and the European Medicines Agency (EMA) decided to approve Rubraca as a maintenance treatment for women with recurrent ovarian cancer.

The randomized, double-blind, placebo-controlled ARIEL 3 Phase 3 trial (NCT01968213) focused on assessing the effects of long-term maintenance therapy with Rubraca in 564 women with recurrent ovarian cancer who had previously responded to platinum-based chemotherapy.

The trial’s findings revealed that maintenance therapy with Rubraca prolonged the time participants lived without disease worsening from 5.4 to 10.8 months, reducing the risk of death or disease progression by 64% compared with a placebo.

Now, Clovis presents new findings from an exploratory analysis of ARIEL 3 focused on assessing the efficacy of Rubraca based on patients’ best response to prior platinum-based chemotherapy.

The subgroup analysis included two large groups of patients: those who had a complete response (CR), or complete cancer eradication while receiving platinum-based chemotherapy; and those who had a partial response (PR), or partial cancer eradication, also while receiving platinum-based chemotherapy.

Within each group, there were different subgroups based on patients’ BRCA status. Response to maintenance treatment with Rubraca also was assessed in women with non-measurable disease — those whose lesions were less than 10 millimeters — at the start of the study (baseline).

Rubraca significantly increased the time participants lived until disease progression compared with a placebo in both CR (11.1 versus 5.6 months) and PR groups (9.0 versus 5.3 months) — regardless of their BRCA status — the results showed.

The results also were consistent across different mutational status. That included whether patients had BRCA mutations, high loss of heterozigozity — which normally indicates the loss of tumor-suppressor genes – regardless of BRCA mutations, or in the overall population.

Among those with non-measurable disease at baseline, 22.1% of those treated with Rubraca and 3.6% of those treated with a placebo had experienced a complete response while receiving platinum-based chemotherapy.

The most common severe adverse event reported in the study was anemia. This was more frequent among women who received maintenance treatment with Rubraca compared with those given a placebo, both in the CR (24.0% versus 0%) and PR groups (20.2% versus 0.8%).

“Regardless of response to last platinum-based chemotherapy, rucaparib maintenance treatment significantly improved PFS [progression-free survival] versus placebo across all cohorts. Similar to patients with measurable disease at baseline, CRs were observed in rucaparib-treated patients with nonmeasurable disease. Safety was consistent across the CR and PR subgroups,” the researchers said.

In addition to data from ARIEL 3, Clovis presented new findings from TRITON2 (NCT02952534) at the ESMO 2019 Congress. The TRITON2 trial assessed the effects of Rubraca in men with BRCA-mutated advanced prostate cancer, or other types of harmful mutations associated with metastatic castration-resistant prostate cancer.

“We look forward to presenting an updated look at the TRITON2 prostate cancer data at ESMO, with a primary focus on patient populations with a deleterious BRCA gene mutation, as well as mutations of other homologous recombination repair genes,” Patrick J. Mahaffy, Clovis’ president and CEO, said in a press release. “We continue to prepare to file a supplemental NDA for Rubraca in BRCA-mutant advanced prostate cancer by the end of the year.”