TY  - JOUR
VL  - 26
JF  - Clinical Cancer Research
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
TI  - A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
UR  - https://doi.org/10.1158/1078-0432.CCR-19-1638
Y1  - 2020/03//
ID  - discovery10092744
AV  - public
IS  - 5
EP  - 1016
SP  - 1009
N2  - 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.
A1  - Oza, AM
A1  - Matulonis, UA
A1  - Alvarez Secord, A
A1  - Nemunaitis, J
A1  - Roman, LD
A1  - Blagden, SP
A1  - Banerjee, S
A1  - McGuire, WP
A1  - Ghamande, S
A1  - Birrer, MJ
A1  - Fleming, GF
A1  - Markham, MJ
A1  - Hirte, HW
A1  - Provencher, DM
A1  - Basu, B
A1  - Kristeleit, R
A1  - Armstrong, DK
A1  - Schwartz, B
A1  - Braly, P
A1  - Hall, GD
A1  - Nephew, KP
A1  - Jueliger, S
A1  - Oganesian, A
A1  - Naim, S
A1  - Hao, Y
A1  - Keer, H
A1  - Azab, M
A1  - Matei, D
SN  - 1078-0432
ER  -