A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.
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Authors
Matulonis, Ursula A
Alvarez Secord, Angeles
Nemunaitis, John
Roman, Lynda D
Banerjee, Susana
McGuire, William P
Ghamande, Sharad
Birrer, Michael J
Fleming, Gini F
Provencher, Diane M
Kristeleit, Rebecca
Armstrong, Deborah K
Schwartz, Benjamin
Braly, Patricia
Nephew, Kenneth P
Jueliger, Simone
Oganesian, Aram
Naim, Sue
Hao, Yong
Keer, Harold
Azab, Mohammad
Matei, Daniela
Publication Date
2020-03Journal Title
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN
1078-0432
Publisher
American Association for Cancer Research
Volume
26
Issue
5
Pages
1009-1016
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Oza, A. M., Matulonis, U. A., Alvarez Secord, A., Nemunaitis, J., Roman, L. D., Blagden, S. P., Banerjee, S., et al. (2020). A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research, 26 (5), 1009-1016. https://doi.org/10.1158/1078-0432.ccr-19-1638
Abstract
PURPOSE: Platinum resistance in ovarian cancer (OC) is associated with epigenetic modifications. Hypomethylating agents (HMAs) have been studied as carboplatin re-sensitizing agents in OC. This randomized phase 2 trial compared guadecitabine, a second generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant OC. EXPERIMENTAL DESIGN: Patients received either G+C (guadecitabine 30 mg/m2 SC once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.
Keywords
Humans, Ovarian Neoplasms, Neoplasm Recurrence, Local, Polyethylene Glycols, Azacitidine, Paclitaxel, Carboplatin, Topotecan, Doxorubicin, Deoxycytidine, Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Survival Rate, Epigenesis, Genetic, Drug Resistance, Neoplasm, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Patient Safety
Identifiers
External DOI: https://doi.org/10.1158/1078-0432.ccr-19-1638
This record's URL: https://www.repository.cam.ac.uk/handle/1810/300177
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