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Association details:
Biomarker:RAD51D mutation
Cancer:Ovarian Cancer
Drug:Rubraca (rucaparib) (PARP inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

80 - Postprogression outcomes in patients with ovarian carcinoma associated with a mutation in a non-BRCA homologous recombination repair gene receiving rucaparib maintenance treatment: Results from the phase III study ARIEL3

Published date:
03/31/2020
Excerpt:
In the rucaparib group, 28 patients (7.5%) had a mutation in a non-BRCA HRR gene, most commonly in RAD51C or RAD51D (RAD51C/D, n = 10). In the placebo group, 15 patients (7.9%) had a non-BRCA HRR gene mutation, most commonly in BRIP1 (n = 5) and RAD51C/D (n = 3). Among patients with a tumor associated with a RAD51C/D mutation, there was significantly longer PFS in those receiving rucaparib than in those receiving placebo (log rank P value, 0.0184); 9/10 rucaparib versus 0/3 placebo patients were progression-free at 12 months....Mutations in a subset of HRR genes, such as RAD51C/D, may confer greater sensitivity to PARP inhibitor treatment.
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Participants With a Solid Tumor (SEASTAR)

Excerpt:
...- Solid tumor, advanced or metastatic, progressed on standard treatment participants in Arm B must have either triple negative breast cancer OR urothelial carcinoma OR ovarian cancer OR have a solid tumor with a deleterious mutation in BRCA1, BRCA2, PALB2, RAD51C or RAD51D...
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Characterization of patients with long-term responses to rucaparib treatment in recurrent ovarian cancer

Published date:
09/30/2021
Excerpt:
This post hoc analysis pooled patients from Study 10 (NCT01482715; Parts 2A and 2B; n = 54) and ARIEL2 (NCT01891344; Parts 1 and 2; n = 491). Overall, 25.3% (138/545) of enrolled patients were responders. Of these, 27.5% (38/138) had long-term responses; 28.3% (39/138) were intermediate- and 34.8% (48/138) were short-term responders. Among responders with BRCA wild-type HGOC, most long- and intermediate-term responders had high genome-wide LOH: 81.8% (9/11) and 76.9% (10/13), respectively, including 7 with deleterious RAD51C, RAD51D, or CDK12 mutations. Among patients who responded to rucaparib, a substantial proportion achieved responses lasting ≥1 year. These analyses demonstrate the relationship between DOR to PARP inhibitor treatment and molecular characteristics in HGOC, such as presence of reversion-resistant BRCA structural variants.
DOI:
10.1016/j.ygyno.2021.08.030
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian cancer (HGOC).

Published date:
05/19/2021
Excerpt:
Pts were randomized 2:1 to receive rucaparib...Among other biomarkers, RAD51C/D mutations were associated with exceptional benefit; low genome-wide loss of heterozygosity was enriched within the ST subgroup...Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of HGOC pts.
DOI:
10.1200/JCO.2021.39.15_suppl.5537
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Characterization of patients (pts) with long-term responses to rucaparib in recurrent ovarian cancer (OC).

Published date:
05/13/2020
Excerpt:
...pts with BRCA homozygous deletion or rearrangement had significantly longer DOR than pts with other mutation types (median 3.5 vs 0.6 y; HR = 0.30; p = 0.024)....Ten of the 13 long-term responders with BRCA wild-type OC had high genome-wide LOH (≥16% LOH), a genomic scar indicative of homologous recombination deficiency, including OC associated with BRCA1 hypermethylation (n = 2) and RAD51C/D mutations (n = 2).
DOI:
10.1200/JCO.2020.38.15_suppl.6015