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

Amit M. Oza, Ursula A. Matulonis, Angeles Alvarez Secord, John Nemunaitis, Lynda D. Roman, Sarah P. Blagden, Susana Banerjee, William P. McGuire, Sharad Ghamande, Michael J. Birrer, Gini F. Fleming, Merry Jennifer Markham, Hal W. Hirte, Diane M. Provencher, Bristi Basu, Rebecca Kristeleit, Deborah K. Armstrong, Benjamin Schwartz, Patricia Braly, Geoff D. HallKenneth P. Nephew, Simone Jueliger, Aram Oganesian, Sue Naim, Yong Hao, Harold Keer, Mohammad Azab, Daniela Matei

Research output: Contribution to journalArticle

6 Scopus citations

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 (GþC) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. Patients and Methods: Patients received either GþC (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 GþC and 49 received TC, of which 27 crossed over to GþC. 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 GþC and TC groups, respectively; P ¼ 0.07). However, the 6-month PFS rate was significantly higher in the GþC group (37% vs. 11% in TC group; P ¼ 0.003). The incidence of grade 3 or higher toxicity was similar in GþC and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the GþC group. Conclusions: Although this trial did not show superiority for PFS of GþC versus TC, the 6-month PFS increased in GþC treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.

Original languageEnglish (US)
Pages (from-to)1009-1016
Number of pages8
JournalClinical Cancer Research
Volume26
Issue number5
DOIs
StatePublished - Mar 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Oza, A. M., Matulonis, U. A., Secord, A. A., Nemunaitis, J., Roman, L. D., Blagden, S. P., Banerjee, S., McGuire, W. P., Ghamande, S., Birrer, M. J., Fleming, G. F., Markham, M. J., Hirte, H. W., Provencher, D. M., Basu, B., Kristeleit, R., Armstrong, D. K., Schwartz, B., Braly, P., ... Matei, D. (2020). A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer. Clinical Cancer Research, 26(5), 1009-1016. https://doi.org/10.1158/1078-0432.CCR-19-1638