RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated...for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-) associated advanced ovarian cancer who have been treated with two or more chemotherapies.

Newly Diagnosed Ovarian Cancer….Recommendation 2.1...For those with germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes, options should include olaparib (300 mg orally every 12 hours for 2 years), niraparib (200-300 mg orally daily for 3 years) or rucaparib (600 mg twice a day for 2 years).

Recurrent Ovarian Cancer: Second-Line or Greater Maintenance and Treatment...Treatment with a PARPi should be offered to patients with recurrent EOC who have not already received a PARPi and have a germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes....Options include:....rucaparib 600 mg every 12 hours;...

...NCCN Panel recommends single-agent rucaparib as recurrence therapy for patients with platinum-sensitive or platinum-resistant ovarian cancer who have been treated with 2 or more lines of chemotherapy and have BRCA mutations (detected as previously described). Maintenance Therapy….Rucaparib added as an option for BRCA1/2 wild-type or unknown and germline or somatic BRCA1/2 mutation.

For patients with recurrent platinum-sensitive ovarian cancer and a BRCA mutation unable to receive platinum-based therapy, rucaparib monotherapy is an option.

In the efficacy population (220 patients in the rucaparib group; 105 in the chemotherapy group), median progression-free survival was 7·4 months (95% CI 7·3-9·1) in the rucaparib group versus 5·7 months (5·5-7·3) in the chemotherapy group (hazard ratio [HR] 0·64 [95% CI 0·49-0·84]; p=0·0010). In the intention-to-treat population (233 in the rucaparib group; 116 in the chemotherapy group), median progression-free survival was 7·4 months (95% CI 6·7-7·9) in the rucaparib group versus 5·7 months (5·5-6·7) in the chemotherapy group (HR 0·67 [95% CI 0·52-0·86]; p=0·0017)....Results from the ARIEL4 study support rucaparib as an alternative treatment option to chemotherapy for patients with relapsed, BRCA1-mutated or BRCA2-mutated ovarian carcinoma.

Across subgroups, significantly longer median PFS was observed with rucaparib versus placebo in the BRCA-mutated and HRD cohorts....Significant extensions in PFS with rucaparib versus placebo were also observed in the BRCA-mutated cohort (3.1- and 3.2-fold longer median PFS in the CR and PR subgroups; Figures 1A, 2A, and 2D)...

Of 564 patients, 79/375 (21%) in the rucaparib arm and 4/189 (2%) in the placebo arm showed exceptional benefit. Within the rucaparib arm, exceptional benefit patients had more favorable clinical prognostic factors at baseline versus the short-term subgroup...BRCA mutations were enriched in the rucaparib exceptional benefit subgroup....Our results suggest rucaparib can deliver exceptional benefit to a diverse set of patients with HGOC.

CONTRADICTING EVIDENCE: In an exploratory analysis of pts with BRCA reversion mutations, median PFS was shorter with rucaparib (n=13) vs CT (n=10); 2.9 vs 5.5 months, hazard ratio 2.769 (95% CI, 0.989–7.755). ORR was not significantly different between the rucaparib and CT arms in both populations....This is the first prospective report from a randomized trial demonstrating that the presence of a BRCA reversion mutation predicts for primary resistance to rucaparib.

In the intent-to-treat population, median investigator-assessed progression-free survival was 8.2 months with rucaparib versus 4.1 months with placebo (n=151 vs n=76; HR 0.33, 95% CI 0.24 to 0.46, p<0.0001)...Across subgroups, median progression-free survival was also significantly longer with rucaparib versus placebo in the BRCA-mutant and homologous recombination deficient cohorts...Rucaparib maintenance treatment significantly improved progression-free survival versus placebo irrespective of progression-free interval following penultimate platinum, number of lines of prior chemotherapy, and previous use of bevacizumab.

Efficacy endpoints were explored in patients with a confirmed BRCA mutation (patients with a reversion mutation were excluded), based on the randomization strata of platinum sensitivity...PFS and objective response rates (ORR) per RECIST v1.1 for rucaparib vs CT across subgroups are presented in the Table...Results from this exploratory subgroup analysis suggest that rucaparib is a reasonable treatment option for heavily pretreated patients across all platinum sensitivity subgroups.

Patients with BRCA-mutated advanced, relapsed OC who received rucaparib had a significant improvement in PFS vs SOC CT.

...Clovis Oncology, Inc. (NASDAQ: CLVS), today announced topline data from the randomized Phase 3 ARIEL4 study of Rubraca, which met its primary endpoint of improved investigator-assessed progression-free survival (InvPFS) compared to chemotherapy in relapsed ovarian cancer patients with a tumor mutation of BRCA who have received two or more prior lines of chemotherapy.

Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]).

...median CFI was 14·3 months (95% CI 13·0-17·4) in the rucaparib group versus 8·8 months (8·0-10·3) in the placebo group (hazard ratio [HR] 0·43 [95% CI 0·35-0·53]; p<0·0001), median TFST was 12·4 months (11·1-15·2) versus 7·2 months (6·4-8·6; HR 0·43 [0·35-0·52]; p<0·0001), median PFS2 was 21·0 months (18·9-23·6) versus 16·5 months (15·2-18·4; HR 0·66 [0·53-0·82]; p=0·0002), and median TSST was 22·4 months (19·1-24·5) versus 17·3 months (14·9-19·4; HR 0·68 [0·54-0·85]; p=0·0007). CFI, TFST, PFS2, and TSST were also significantly longer with rucaparib than placebo in the BRCA-mutant and homologous recombination-deficient cohorts.

...Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA mutation...

Patients received oral rucaparib 600 mg twice daily (starting dose)….ORR was 59.3% (95% CI 45.0-72.4%)….In patients with relapsed, platinum-sensitive or platinum-resistant germline BRCA-mutant high-grade ovarian cancer who had received ≥2 prior chemotherapies, rucaparib had robust antitumour activity with a safety profile consistent with prior reports.

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.

To describe molecular and clinical characteristics of patients with high-grade recurrent ovarian carcinoma (HGOC) who had long-term responses to the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib....Most of the long-term responders harbored a BRCA1 or BRCA2 (BRCA) mutation (71.1%, 27/38), and BRCA structural variants were most frequent among long-term responders (14.8%; 4/27).

...491 patients were enrolled and received rucaparib in ARIEL2….confirmed objective response rates (ORR), the study’s primary endpoint, were 31.0% (95% confidence interval [CI], 21.3–42.0), 6.8% (95% CI, 2.3–15.3), and 5.6% (95% CI, 2.1–11.8), respectively, in patients with BRCAmut, BRCAwt/LOH-high, and BRCAwt/LOH-low HGOC (Supplementary Table S2), with durable responses seen across HRD subgroup...

In exposure-efficacy analyses of patients with a BRCA mutation (n = 102), AUCss was positively associated with independent radiologist reviewer (IRR)-assessed ORR in platinum-sensitive (n = 75, P = 0.017) but not platinum-resistant (n = 27, P = 0.661).Higher rucaparib AUCss was associated with improved IRR-assessed response in platinum-sensitive, BRCA-mutated rOC.

Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup...Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p<0·0001)…