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Targeted therapy

ARIEL3 — broad benefit of PARP inhibitors in ovarian cancer

Nature Reviews Clinical Oncology volume 14, page 713 (2017)Cite this article

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In ARIEL3, 564 women with high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma and an objective response to second-line or later-line platinum-based chemotherapy were randomly assigned 2:1 to receive rucaparib or placebo. In addition to the overall efficacy and safety of treatment, a test of genome-wide loss of heterozygosity (LOH) — a marker of homologous recombination deficiency (HRD) — was prospectively evaluated as a predictive biomarker. “While patients with any genotype were enrolled, the analysis was designed to assess efficacy in a 'step-down' fashion including sequentially larger cohorts of patients,” explains lead author Robert Coleman.

In the smallest of three nested cohorts, comprising only women with germ-line or somatic BRCA mutations, the median progression-free survival (PFS) duration was 16.6 months with rucaparib, compared with 13.6 months in the larger LOH-high (HRD) disease cohort, and 10.8 months in the intention-to-treat population (versus 5.4 months with placebo in each cohort). Coleman adds: “the most compelling finding is that rucaparib delayed disease progression across prespecified subgroups — those we expected to benefit (women with somatic BRCA alterations or BRCA-wild-type, LOH-high disease), as well as those we didn't (patients with LOH-low tumours).” Notably, 12-month PFS in women with BRCA-wild-type, LOH-low tumours was <5% with placebo, but >30% with rucaparib.

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References

  1. Coleman, R. L. et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet http://dx.doi.org/10.1016/S0140-6736(17)32440-6 (2017)

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  1. David Killock
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Killock, D. ARIEL3 — broad benefit of PARP inhibitors in ovarian cancer. Nat Rev Clin Oncol 14, 713 (2017). https://doi.org/10.1038/nrclinonc.2017.161

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