Research & Development
Clovis Oncology Presents Patient-Centered Outcomes Data from Phase 3 ARIEL3 Study for Rubraca in Advanced Ovarian Cancer
22 May 2019 - - Data demonstrating that patients with recurrent ovarian cancer who received Rubraca in the Phase 3 ARIEL3 study had longer periods of quality-adjusted time without clinically relevant symptoms as compared to patients who received placebo, and that Rubraca maintenance treatment continued to provide significant benefit in progression-free survival when weighted with patients' perceptions of their wellbeing, US-based biopharmaceutical company Clovis Oncology, Inc. (NASDAQ: CLVS) said.

The presentation at the International Society for Pharmacoeconomics and Outcomes (ISPOR) annual meeting in New Orleans highlights post-hoc evaluations of quality-adjusted time without symptoms or toxicity (Q-TWiST) and quality-adjusted PFS (QA-PFS) from the randomised, placebo-controlled study of Rubraca (rucaparib) for the maintenance treatment of patients with recurrent ovarian cancer.

To the company's knowledge, this is the first time that Q-TWiST data will be presented in the maintenance therapy setting in recurrent ovarian cancer.

During the study, patients were asked to complete EuroQol's five-dimension, three-level (EQ-5D-3L) questionnaire at screening, on day 1 of each treatment cycle, at the treatment discontinuation visit, and at the 28-day follow-up visit.

QA-PFS and Q-TWiST analyses were calculated using EQ-5D-3L data as described in the poster.

Patient-centered outcomes were examined in the intent-to-treat population (all randomized patients), in patients with a BRCA mutation, and in subgroups of patients with BRCA wild-type carcinomas based on loss of heterozygosity status (BRCA wild type/LOH high; BRCA wild type/LOH low; and BRCA wild type/LOH indeterminate).

In the study, mean QA-PFS was significantly longer in the Rubraca arm than placebo arm (12.02 vs 5.74 months) for the ITT population and for patients with a BRCA mutation (15.28 vs. 5.92 months).

In patients with a BRCA wild-type carcinoma, mean QA-PFS was longer in the Rubraca arm than the placebo arm regardless of LOH status.

Mean Q-TWiST analysis using all grade ≥3 treatment-emergent adverse events (TEAEs) was significantly longer in the rucaparib arm than placebo for the ITT population (13.32 vs 6.44 months) and for patients with a BRCA mutation (16.42 vs 6.70 months).

In the analyses using TEAEs of interest (grade ≥2 TEAEs of nausea, vomiting, fatigue, and asthenia), Q-TWiST was also longer in the rucaparib arm than placebo for the ITT population (13.16 vs 6.40 months) and for patients with BRCA mutation (16.24 vs 6.68 months).

In patients with BRCA wild-type carcinoma, longer Q-TWiST was also observed in the Rubraca treated arm, regardless of LOH status.

The Rubraca ISPOR poster will be available online at http://clovisoncology.com/pipeline/scientific-presentations/ as of the time it is presented at the meeting.

QA-PFS represents the duration of survival without disease progression, adjusted for the value the patient placed on their health status i.e. it is a survival measure that adjusts for patient perceptions of treatment toxicity and any associated detrimental effects.

Q-TWiST results were derived by subtracting from the survival endpoint all time in which patients experienced treatment toxicity or disease symptoms, and then multiplying this area under the curve by a patient-derived utility value.

Q-TWiST therefore adds additional value not available in a traditional TWiST analysis because it reflects patients' perceptions of the impact of toxicity on the survival endpoint.

The ARIEL3 pivotal study of rucaparib is a confirmatory randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance treatment to platinum-sensitive ovarian cancer patients can extend the period of time for which the disease is controlled after a complete or partial response to platinum-based chemotherapy. The study enrolled 564 patients with high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer.

To be eligible for the study, participants had to have received at least two prior platinum-based treatment regimens, been sensitive to the penultimate platinum regimen, and achieved a complete or partial response to their most recent platinum-based regimen.

There were no genomic selection criteria for this study. Trial participants were randomised 2: 1 to receive 600 milligrams of rucaparib twice daily or placebo.

The study achieved its primary endpoint of improved PFS by investigator review in each of three populations. PFS was also improved in the rucaparib group compared with placebo by independent review, a key secondary endpoint, in all three populations.

In addition, rucaparib improved objective response rate vs placebo among evaluable trial participants in all three study populations.

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutations (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Clovis Oncology is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the US, Europe and additional international markets.
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