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.

...- 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...

Adult women with HGOC, fallopian tube, or primary peritoneal cancer were included and received rucaparib (600 mg BID) in the MTN, Tx Pt-sensitive or Tx Pt-resistant setting....In the Tx group, 10 patients (30.3%) were LTR, with a median age of 71 years (47-86). All of them harbored BRCA and/or RAD51C mutations.

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.

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.

...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).