Oza, AM;
Tinker, AV;
Oaknin, A;
Shapira-Frommer, R;
McNeish, IA;
Swisher, EM;
Ray-Coquard, I;
... Kristeleit, RS; + view all
(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.
10.1016/j.ygyno.2017.08.022.
Preview |
Text
Kristeleit_1-s2.0-S009082581731260X-main.pdf - Published Version Download (1MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | 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 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ygyno.2017.08.022 |
| Publisher version: | https://doi.org/10.1016/j.ygyno.2017.08.022 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | 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 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1574279 |
Archive Staff Only
 |
View Item |
