medwireNews: Maintenance therapy with the PARP inhibitor rucaparib offers significantly longer progression-free survival (PFS) than placebo for women with advanced platinum-sensitive ovarian cancer, indicate ARIEL3 trial findings reported at the ESMO 2017 Congress in Madrid, Spain.
The patients had all previously received a median of two lines of platinum-based chemotherapy for high-grade ovarian, fallopian tube or primary peritoneal cancer, and had achieved a complete or partial response to their latest regimen before entering the phase III trial.
Step-down analysis demonstrated that the 196 trial participants who carried a germline or somatic BRCA mutation derived the most benefit from rucaparib 600 mg twice daily, with a median progression-free survival (PFS) of 16.6 months versus 5.4 months for placebo, giving a significant hazard ratio (HR) of 0.23.
PFS was also longer with rucaparib than placebo among the 354 patients with homologous recombination deficiency (HRD) regardless of BRCA status, including those with a high degree of genomic loss of heterozygosity (LOH), and the total population of 564 patients including patients with neither BRCA mutations nor HRD.
Median PFS for patients given rucaparib in these groups was 13.6 and 10.8 months, respectively, with corresponding HRs of 0.32 and 0.36, reported
Presenting the findings, Jonathan Ledermann, from University College London, UK, also reported an exploratory analysis for ARIEL3 showing that the primary endpoint was also achieved for the 158 patients who were classified as wild-type for BRCA and high LOH (median PFS of 9.7 months, HR=0.44) and for the 161 patients who had wild-type BRCA and low LOH (median PFS of 6.7 months, HR=0.58).
Safety analysis showed side effects were similar to those previously reported for rucaparib, most commonly nausea (75.3%), asthenia (69.4%), dysgeusia (39.2%). Ledermann emphasized that these events were mostly low grade with “relatively few” patients experiencing grade 3 adverse events.
And although a third (33.9%) of patients experienced liver enzyme elevation, most cases were transient and asymptomatic, he said.
“The results of ARIEL3 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,” the presenter concluded.
Overall survival and patient-reported health outcome results will be reported for ARIEL3 at a later date, Ledermann added.
The findings were published simultaneously in The Lancet.
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