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A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.


ABSTRACT: 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/m2 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.

SUBMITTER: Oza AM 

PROVIDER: S-EPMC7056559 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

Oza Amit M AM   Matulonis Ursula A UA   Alvarez Secord Angeles A   Nemunaitis John J   Roman Lynda D LD   Blagden Sarah P SP   Banerjee Susana S   McGuire William P WP   Ghamande Sharad S   Birrer Michael J MJ   Fleming Gini F GF   Markham Merry Jennifer MJ   Hirte Hal W HW   Provencher Diane M DM   Basu Bristi B   Kristeleit Rebecca R   Armstrong Deborah K DK   Schwartz Benjamin B   Braly Patricia P   Hall Geoff D GD   Nephew Kenneth P KP   Jueliger Simone S   Oganesian Aram A   Naim Sue S   Hao Yong Y   Keer Harold H   Azab Mohammad M   Matei Daniela D  

Clinical cancer research : an official journal of the American Association for Cancer Research 20191212 5


<h4>Purpose</h4>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.<h4>Patients and methods</h4>Patients received either G+C (guadecitabine 30 mg/m<sup>2</sup  ...[more]

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