NRG-GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer.

Autor: Rimel BJ; Division of Gynecologic Oncology, Cedars-Sinai Medical Center, Los Angeles, California, USA., Enserro D; Clinical Trials Development Division, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA., Bender DP; University of Iowa Hospitals & Clinics, Iowa City, Iowa, USA., Jackson CG; University of Oklahoma Health Sciences Center, Mercy Hospital Gynecologic Oncology, Oklahoma City, Oklahoma, USA., Tan A; Minnesota Oncology, Coon Rapids, Minnesota, USA., Alluri N; St. Luke's Cancer Institute, Boise, Idaho, USA., Borowsky M; Hackensack Meridian Health, Neptune, New Jersey, USA., Moroney J; University of Chicago Medicine, Schererville, Indiana, USA., Hendrickson AW; Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota, USA., Backes F; The Ohio State University Comprehensive Cancer Center, Ohio State Internal Medicine, Hilliard, Ohio, USA., Swisher E; University of Washington Medical Center, Seattle, Washington, USA., Powell M; Washington University School of Medicine, St. Louis, Missouri, USA., MacKay H; Division of Medical Oncology & Hematology, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2024 Apr 15; Vol. 130 (8), pp. 1234-1245. Date of Electronic Publication: 2023 Dec 21.
DOI: 10.1002/cncr.35151
Abstrakt: Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
(© 2023 American Cancer Society.)
Databáze: MEDLINE
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