Journal article
NRG-GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer
Cancer, Vol.130(8), pp.1234-1245
04/15/2024
DOI: 10.1002/cncr.35151
PMCID: PMC11168450
PMID: 38127487
Abstract
This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer.
This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel.
A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response.
The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity.
Details
- Title: Subtitle
- NRG-GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer
- Creators
- Bobbie J Rimel - Cedars-Sinai Medical CenterDanielle Enserro - Clinical Trials Development Division, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USADavid P Bender - University of IowaCamille Gunderson Jackson - University of Oklahoma Health Sciences CenterAnnie Tan - Minnesota OncologyNitya Alluri - St. Luke’s Boise Medical CenterMark Borowsky - Hackensack Meridian HealthJohn Moroney - University of ChicagoAndrea E. Wahner Hendrickson - Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota, USAFloor Backes - The Ohio State UniversityElizabeth Swisher - University of Washington Medical CenterMatthew Powell - Washington University School of Medicine, St. Louis, Missouri, USAHelen MacKay - Sunnybrook Health Science Centre
- Resource Type
- Journal article
- Publication Details
- Cancer, Vol.130(8), pp.1234-1245
- DOI
- 10.1002/cncr.35151
- PMID
- 38127487
- PMCID
- PMC11168450
- NLM abbreviation
- Cancer
- eISSN
- 1097-0142
- Grant note
- NRG Oncology
- Language
- English
- Electronic publication date
- 12/21/2023
- Date published
- 04/15/2024
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984533287102771
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