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A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24
NSGO, Denmark; Rigshosp, Denmark.
Odense Univ Hosp, Denmark.
Rigshosp, Denmark.
NSGO, Denmark; Univ Southern Denmark, Denmark.
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2019 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 84, no 4, p. 791-798Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 84, no 4, p. 791-798
Keywords [en]
Niraparib; PARP inhibitor; Ovarian cancer; Bevacizumab; BRCA
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-161404DOI: 10.1007/s00280-019-03917-zISI: 000488659900012PubMedID: 31375879OAI: oai:DiVA.org:liu-161404DiVA, id: diva2:1367449
Note

Funding Agencies|Tesaro Inc.; NSGO

Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-04

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Åvall Lundqvist, Elisabeth
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Oncology
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