A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24
Research output: Contribution to journal › Journal article › Research › peer-review
BACKGROUND: Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial.
MATERIALS AND METHODS: In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D).
RESULTS: Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21.
CONCLUSIONS: There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.
Original language | English |
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Journal | Cancer Chemotherapy and Pharmacology |
Volume | 84 |
Issue number | 4 |
Pages (from-to) | 791-798 |
Number of pages | 8 |
ISSN | 0344-5704 |
DOIs | |
Publication status | Published - 2019 |
- Adult, Angiogenesis Inhibitors/administration & dosage, Antineoplastic Agents/administration & dosage, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab/administration & dosage, Carcinoma, Ovarian Epithelial/drug therapy, Dose-Response Relationship, Drug, Drug Monitoring/methods, Female, Humans, Indazoles/administration & dosage, Middle Aged, Ovarian Neoplasms/drug therapy, Piperidines/administration & dosage, Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage, Progression-Free Survival
Research areas
ID: 241644144