Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 and ARIEL2.
File(s)
Published version
Accepted version
Author(s)
Type
Journal Article
Abstract
OBJECTIVE: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). METHODS: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600mg BID, irrespective of BRCA1/2 mutation status and prior treatments. RESULTS: In the efficacy population (n=106), ORR was 53.8% (95% confidence interval [CI], 43.8-63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2months (95% CI, 6.6-11.6). In the safety population (n=377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile.
Date Issued
2017-09-04
Date Acceptance
2017-08-20
Citation
Gynecologic Oncology, 2017, 147 (2), pp.267-275
ISSN
0090-8258
Publisher
Elsevier
Start Page
267
End Page
275
Journal / Book Title
Gynecologic Oncology
Volume
147
Issue
2
Copyright Statement
© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
PII: S0090-8258(17)31260-X
Subjects
Ovarian carcinoma
PARP inhibitor
Rucaparib
Somatic, germline BRCA mutation
Adult
Aged
Aged, 80 and over
BRCA1 Protein
BRCA2 Protein
Female
Genes, BRCA1
Genes, BRCA2
Germ-Line Mutation
Humans
Indoles
Middle Aged
Neoplasm Grading
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
Publication Status
Published