Women with recurrent, platinum-sensitive ovarian cancer lived twice as long without disease progression when they received maintenance therapy with the PARP inhibitor rucaparib (Rubraca), a randomized trial showed.
Overall, patients treated with rucaparib had a median progression-free survival of 10.8 months compared with 5.4 months for the placebo group. The magnitude of the benefit tripled for patients with BRCA-mutant ovarian cancer — 16.6 versus 5.4 months for placebo-treated patients.
A subgroup analysis showed a consistent treatment effect of the PARP inhibitor across all prespecified patient groups, as reported here at the European Society for Medical Oncology congress.
“The results of the ARIEL3 trial demonstrate the benefit of rucaparib maintenance treatment for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy,” said Jonathan Ledermann, MD, of University College London.
“Rucaparib maintenance treatment significantly improved progression-free survival versus placebo in the nested BRCA-mutant, homologous recombination-deficient cohorts, and in the overall intention-to-treat population,” he added. “Several patients with measureable residual disease at baseline had further reduction in tumor burden with rucaparib maintenance treatment. The most common side effects were gastrointestinal, asthenia, and anemia, consistent with prior studies of rucaparib.”
The results added to a growing volume of evidence supporting the use of PARP to treat recurrent ovarian cancer.
Earlier this year, the ARIEL2 trial of rucaparib established efficacy across a broad range of patients with recurrent, platinum-sensitive ovarian cancer. Results of another randomized trial showed almost a fourfold improvement in PFS in patients with platinum-sensitive ovarian cancer treated with olaparib (Lynparza) maintenance therapy. Late last year, a randomized trial of niraparib (Zejula) maintenance therapy showed a PFS benefit, regardless of BRCA mutation status.
“We have data from three PARP inhibitors in the same setting, and we have no data to say that one is better than the others,” said invited discussant Sandro Pignata, MD, of the University of Naples in Italy.
Instead, adverse events might prove to be the distinguishing feature of the agents. Rucaparib is the only one of the three drugs in the class associated with liver toxicity. Niraparib is associated with substantially more thrombocytopenia and leukopenia as compared with rucaparib and olaparib. Fatigue, nausea, and anemia occur with similar frequency across the three drugs.
Rucaparib and niraparib are associated with higher rates of treatment interruption, dose reduction, and discontinuation due to adverse events.
“These are clinical factors. What happens in clinical practice?” said Pignata. “I think we need to collect data from real-life studies to see how dose adjustments can be performed and how the toxicity affects our patients, and mainly, we need to learn how to treat the side effects.”
“Peak toxicity probably is not the best way to describe safety,” he added. “The duration [of toxicity] and changes after dose adjustment probably are more important.”
The ARIEL3 trial continued the line of clinical investigation that helped to define patients who benefit from treatment with rucaparib. Previous studies in patients with recurrent ovarian cancer demonstrated rucaparib efficacy in patients with BRCA mutations and those with tumors harboring a higher percentage of loss of heterozygosity (LOH), a marker of homologous repair deficiency (HRD).
ARIEL3 investigated rucaparib in a population of patients with high-grade recurrent ovarian cancer that had responded to second-line or later platinum-based chemotherapy. Patients were randomized 2:1 to rucaparib or placebo maintenance therapy and followed until disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS). In addition to an intention-to-treat analysis, investigators assessed rucaparib efficacy in patients with BRCA-mutant disease and with tumors exhibiting HRD.
Data analysis comprised 564 patients, 196 of whom had BRCA-mutant ovarian cancer. The HRD cohort comprised 354 patients (including the BRCA-mutant subgroup).
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