%0 Journal Article
%@ 1078-0432
%A Oza, AM
%A Matulonis, UA
%A Alvarez Secord, A
%A Nemunaitis, J
%A Roman, LD
%A Blagden, SP
%A Banerjee, S
%A McGuire, WP
%A Ghamande, S
%A Birrer, MJ
%A Fleming, GF
%A Markham, MJ
%A Hirte, HW
%A Provencher, DM
%A Basu, B
%A Kristeleit, R
%A Armstrong, DK
%A Schwartz, B
%A Braly, P
%A Hall, GD
%A Nephew, KP
%A Jueliger, S
%A Oganesian, A
%A Naim, S
%A Hao, Y
%A Keer, H
%A Azab, M
%A Matei, D
%D 2020
%F discovery:10092744
%J Clinical Cancer Research
%N 5
%P 1009-1016
%T A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
%U https://discovery.ucl.ac.uk/id/eprint/10092744/
%V 26
%X PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m^{2} s.c. 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.
%Z This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.