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)
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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 |
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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 |
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