A phase II open-label, multicenter study of single-agent rucaparib in the treatment of patients with relapsed ovarian cancer and a deleterious BRCA mutation.
Year: 2015
Type: conference-abstract
Abstract: 5513 Background: Rucaparib is a potent oral PARP inhibitor that has shown robust activity in patients (pts) with homologous recombination deficient (HRD) tumors, with the highest response rates observed in ovarian and breast cancer pts harboring deleterious germline BRCA mutations (gBRCAmut). This phase II study (NCT 01891344) evaluated the efficacy and safety of rucaparib in pts with relapsed gBRCAmut high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC/FTC/PPC). Methods: Women with gBRCAmut EOC/FTC/PPC who received 2-4 prior chemotherapy (chemo) regimens and had a progression-free interval (PFI) ≥ 6 months after their last platinum dose were enrolled. ECOG PS 0-1 and adequate organ function were required. Pts received oral rucaparib 600 mg BID in 21 day cycles until disease progression. The primary endpoint was objective response rate (ORR) by RECIST 1.1. Results: 35 pts have been enrolled. Median age was 55 years (range 44-84). The median number of prior chemo regimens was 2 (range 2– 4). Fifteen pts (43%) had received ≥ 3 prior chemo regimens. RECIST/CA-125 ORR was 81% (21/26); RECIST ORR was 65% (17/26). RECIST ORR was 88% (7/8) and 56% (10/18), respectively, in pts with PFI 6-12 mo or > 12 mos. In pts with ≥ 3 prior chemo regimens, 58% (7/12) achieved a RECIST response. The median duration of response and PFS have not been reached. The most common treatment-related AEs (generally grade 1/2) were nausea (55%), anemia (41%), ALT/AST elevations (41%), fatigue (41%), and asthenia (35%). The ALT/AST elevations are transient with no other evidence of liver dysfunction. No pts discontinued treatment due to an AE. No secondary malignancies have been observed. Conclusions: Rucaparib demonstrated robust activity in heavily pretreated EOC/FTC/PPC pts with gBRCAmut tumors with 81% of pts achieving RECIST/CA-125 responses. Rucaparib was well tolerated and AEs did not result in any treatment discontinuations. The ongoing pivotal program in EOC/FTC/PPC pts is evaluating rucaparib in treatment (ARIEL2, NCT01891344) and maintenance (ARIEL3, NCT01968213) settings. Clinical trial information: NCT01891344.
Source: Journal of Clinical Oncology
Authors: Ronnie Shapira-Frommer, Amit M. Oza, Susan M. Domchek, Judith Balmaña, Manish R. Patel, Lee-may Chen, Yvette Drew, Howard A. Burris, Jacob Korach, Michael Flynn, Valerie Lydia Bowering, Mark Aloysuis Morgan, Simon Paul Watkins, Dayna Simpson, Sandra Goble, Lara Maloney, Rebecca Sophie Kristeleit
Institutions: Sheba Medical Center, University Health Network, Princess Margaret Cancer Centre, Hospital of the University of Pennsylvania, Vall d'Hebron Hospital Universitari, University of California, San Francisco, Freeman Hospital, Sarah Cannon, Tennessee Oncology, University College London, Clovis Oncology (United Kingdom), Clovis Oncology (United States)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4253161128