| 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. © 2017 The Authors |
| Keywords: |
adult; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; major clinical study; somatic mutation; genetics; clinical trial; constipation; fatigue; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; side effect; cancer grading; ovarian neoplasms; progression free survival; phase 2 clinical trial; anemia; nausea; thrombocytopenia; vomiting; pathology; brca1 protein; brca2 protein; abdominal pain; asthenia; dyspnea; tumor suppressor gene; genes, brca1; genes, brca2; ovary carcinoma; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; phase 3 clinical trial; phase 1 clinical trial; ovarian carcinoma; indoles; indole derivative; brca1 protein, human; germ-line mutation; dysgeusia; neoplasms, glandular and epithelial; decreased appetite; germline mutation; parp inhibitor; neoplasm grading; brca2 protein, human; rucaparib; very elderly; humans; human; female; priority journal; article; poly(adp-ribose) polymerase inhibitors; somatic, germline brca mutation
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