Clinical activity of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with high-grade ovarian carcinoma (HGOC) and a BRCA mutation (BRCAmut): Analysis of pooled data from Study 10 (parts 1, 2a, and 3) and ARIEL2 (parts 1 and 2)

Background

Rucaparib has demonstrated clinical activity in BRCA^mut HGOC in two phase 2 studies. Data from these studies were pooled to examine the clinical activity and safety of rucaparib in BRCA^mut pts with HGOC who have received ≥2 prior chemotherapy (chemo) regimens.

Methods

Pts (n = 106) with BRCA^mut relapsed, HGOC who received ≥2 prior chemo regimens and were enrolled in Study 10 part 2a (n = 42) or ARIEL2 part 1 or 2 (n = 64) by 1 Oct 2015 were included in the pooled efficacy analysis. The pooled safety dataset (n = 144) included 38 additional pts with

Results

Median age was 59 years; median number of prior chemo regimens was 3. Median duration of treatment was 6.9 months. The investigator-assessed confirmed objective response rate (RECIST v1.1) was 54% in pts with ≥2 prior chemo regimens. The median duration of investigator-assessed confirmed response was 9.2 months (95% confidence interval: 6.6-11.7). Common treatment-emergent adverse events included asthenia/fatigue (78%; grade ≥3: 15%), nausea (76%; grade ≥3: 4%), anemia (51%; grade ≥3: 27%), vomiting (50%; grade ≥3: 6%), and transient increased ALT/AST (47%; grade ≥3: 13%). Five pts died as a result of disease progression.

Conclusions

Rucaparib has clinical activity and an acceptable safety profile in pts with BRCA^mut HGOC who received ≥2 prior lines of chemo. The efficacy of rucaparib will be compared to standard chemo in a phase 3 study (ARIEL4).

Clinical trial identification

NCT01482715 (NIH), NCT01891344 (NIH)

Legal entity responsible for the study

Clovis Oncology, Inc.

Funding

Clovis Oncology, Inc.

Disclosure

R.S. Kristeleit: Consulting/Advisory role: Clovis Oncology, Roche/Genentech, Sotio, Lytix Biopharma; Travel, Accommodations, Expenses: Clovis Oncology, Basilea, PiQuR; Honoraria: Clovis Oncology, Roche/Genentech, AstraZeneca. A. Oaknin: Consulting or Advisory Role: AstraZeneca, PharmaMar, Clovis Oncology, Roche Glycart J. Balmaña: Consulting or Advisory Role - Clovis Oncology, Inc.; Speakers' Bureau: AstraZeneca; Travel Expenses: AstraZeneca. I.L. Ray-Coquard: Consulting or Advisory Role: PharmaMar, AstraZeneca, MSD, Roche Glycart; Travel, Accommodations, Expenses: PharmaMar, Roche Glycart. S. Domchek: Honoraria: EMD Serono; Research Funding: AstraZeneca, Clovis Oncology, Abbvie, Pharmamar. A.V. Tinker: Consulting or Advisory Role: AstraZeneca; Research Funding: AstraZeneca/MedImmune K. Bell-Mcguinn: Consulting or Advisory Role: Clovis Oncology, AstraZeneca; Travel, Accommodations, Expenses: Abbvie. G. Konecny: Consulting or Advisory Role: Novartis; Travel, Accommodations, Expenses: Novartis; Research Funding: Amgen, Pfizer. H. Giordano, L. Maloney, S. Goble, L. Rolfe: Employment: Clovis Oncology, Inc.; Stock and Other Ownership Interests: Clovis Oncology, Inc. A. Oza: Consulting or Advisory Role: Amgen, Verastem, Clovis Oncology, Immunovaccine; Travel, Accommodations, Expenses: AstraZeneca; Honoraria: WebRx; Research Funding: AstraZeneca, Roche, Merck, AstraZeneca. All other authors have declared no conflicts of interest.