Highlights
- •Clinical/molecular characteristics associated with exceptional benefit from rucaparib maintenance in ARIEL3 were explored.
- •21% of patients in the rucaparib arm derived exceptional benefit (PFS ≥2 years) compared with only 2% in the placebo arm.
- •Clinical characteristics associated with exceptional outcomes on rucaparib were related to platinum sensitivity.
- •BRCA1, BRCA2, RAD51C, and RAD51D mutations were associated with exceptional benefit from rucaparib.
- •A diverse set of patients with high-grade ovarian carcinoma can derive exceptional benefit from rucaparib maintenance.
Abstract
Objective
ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor
rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma
who responded to their latest line of platinum therapy. Rucaparib improved progression-free
survival across all predefined subgroups. Here, we present an exploratory analysis
of clinical and molecular characteristics associated with exceptional benefit from
rucaparib.
Methods
Patients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular
features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association
with exceptional benefit (progression-free survival ≥2 years) versus progression on
first scan (short-term subgroup) and other efficacy outcomes.
Results
Rucaparib treatment was significantly associated with exceptional benefit compared
with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline
clinical characteristics and with carcinomas harboring molecular evidence of homologous
recombination deficiency (HRD). A comparison between patients who derived exceptional
benefit from rucaparib and those in the short-term subgroup revealed both clinical
markers (no measurable disease at baseline, complete response to latest platinum,
longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with
exceptional benefit.
Conclusions
Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with
favorable clinical characteristics or molecular features associated with HRD. Our
results suggest that rucaparib can deliver exceptional benefit to a diverse set of
patients with recurrent high-grade ovarian carcinoma.
Keywords
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Article info
Publication history
Published online: October 20, 2022
Accepted:
August 25,
2022
Received in revised form:
August 22,
2022
Received:
June 16,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc.
