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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Oza, Amit M 
Matulonis, Ursula A 
Alvarez Secord, Angeles 
Nemunaitis, John 
Roman, Lynda D 

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.

Description

Keywords

Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Carboplatin, Deoxycytidine, Doxorubicin, Drug Resistance, Neoplasm, Epigenesis, Genetic, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Ovarian Neoplasms, Paclitaxel, Patient Safety, Polyethylene Glycols, Survival Rate, Topotecan, Treatment Outcome, Gemcitabine

Journal Title

Clin Cancer Res

Conference Name

Journal ISSN

1078-0432
1557-3265

Volume Title

26

Publisher

American Association for Cancer Research (AACR)

Rights

All rights reserved