UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Oza, AM; Matulonis, UA; Alvarez Secord, A; Nemunaitis, J; Roman, LD; Blagden, SP; Banerjee, S; ... Matei, D; + view all (2020) A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer. Clinical Cancer Research , 26 (5) pp. 1009-1016. 10.1158/1078-0432.CCR-19-1638. Green open access

[thumbnail of Guadecitabine and carboplatin in ovarian cancer.pdf]
Preview
Text
Guadecitabine and carboplatin in ovarian cancer.pdf - Accepted Version

Download (406kB) | Preview

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/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.

Type: Article
Title: A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/1078-0432.CCR-19-1638
Publisher version: https://doi.org/10.1158/1078-0432.CCR-19-1638
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10092744
Downloads since deposit
50Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item