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

Oza, A. M. et al. (2017) 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. Gynecologic Oncology, 147(2), pp. 267-275. (doi: 10.1016/j.ygyno.2017.08.022) (PMID:28882436)

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 600 mg 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 600 mg 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 9.2 months (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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcneish, Professor Iain
• Authors: Oza, A. M., Tinker, A. V., Oaknin, A., Shapira-Frommer, R., Mcneish, I. A., Swisher, E. M., Ray-Coquard, I., Bell-McGuinn, K., Coleman, R. L., O’Malley, D. M., Leary, A., Chen, L.-m., Provencher, D., Ma, L., Brenton, J. D., Konecny, G. E., Castro, C. M., Giordano, H., Maloney, L., Goble, S., Lin, K. K., Sun, J., Raponi, M., Rolfe, L., and Kristeleit, R. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Gynecologic Oncology
• Publisher: Elsevier
• ISSN: 0090-8258
• ISSN (Online): 1095-6859
• Published Online: 04 September 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Gynecologic Oncology 147(2): 267-275
• Publisher Policy: Reproduced under a Creative Commons License