Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial

Joyce F. Liu, Mark F. Brady, Ursula A. Matulonis, Austin Miller, Elise C. Kohn, Elizabeth M. Swisher, David Cella, William P. Tew, Noelle G. Cloven, Carolyn Y. Muller, David P. Bender, Richard G. Moore, David P. Michelin, Steven E. Waggoner, Melissa A. Geller, Keiichi Fujiwara, Stacy D. D'Andre, Michael Carney, Angeles Alvarez Secord, Katherine M. MoxleyMichael A. Bookman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

PURPOSE: Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy. PATIENTS AND METHODS: NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada. Eligible patients had high-grade serous or endometrioid platinum-sensitive ovarian cancer. Patients were randomly assigned 1:1:1 to platinum-based chemotherapy, olaparib, or olaparib/cediranib. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included activity within germline BRCA-mutated or wild-type subgroups and patient-reported outcomes (PROs). RESULTS: Between February 04, 2016, and November 13, 2017, 565 eligible patients were randomly assigned. Median PFS was 10.3 (95% CI, 8.7 to 11.2), 8.2 (95% CI, 6.6 to 8.7), and 10.4 (95% CI, 8.5 to 12.5) months with chemotherapy, olaparib, and olaparib/cediranib, respectively. Olaparib/cediranib did not improve PFS versus chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P = .077). In women with germline BRCA mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib/cediranib and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In women without a germline BRCA mutation, the PFS HR versus chemotherapy was 0.97 (95% CI, 0.73 to 1.30) for olaparib/cediranib and 1.41 (95% CI, 1.07 to 1.86) for olaparib. Hematologic adverse events occurred more commonly with chemotherapy; however, nonhematologic adverse events were higher with olaparib/cediranib. In 489 patients evaluable for PROs, patients receiving olaparib/cediranib scored on average 1.1 points worse on the NFOSI-DRS-P subscale (97.5% CI, -2.0 to -0.2, P = .0063) versus chemotherapy; no difference between olaparib and chemotherapy was observed. CONCLUSION: Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. Notably, in patients with a germline BRCA mutation, both olaparib and olaparib/cediranib had significant clinical activity.

Original languageEnglish (US)
Pages (from-to)2138-2147
Number of pages10
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume40
Issue number19
DOIs
StatePublished - Jul 1 2022

Bibliographical note

Funding Information:
The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines, and was approved by the appropriate institutional review board for each participating site. All participants provided written informed consent. The study was sponsored by the US National Cancer Institute (NCI) and registered on ClinicalTrials.gov identifier: NCT02446600 .

Funding Information:
Supported by National Cancer Institute grants to NRG Oncology SDMC (1U10 CA180822), NRG Operations (U10CA180868), and U24CA180803 (IROC). Additionally, Canadian Cancer Trials Group (CCTG) participation in this trial is supported through its grant from the US National Cancer Institute of the National Institutes of Health under the award CA180863. Additional programmatic funding support for the CCTG is provided by the Canadian Cancer Society (#704970) and the Canada Foundation for Innovation. Funding was also received from AstraZeneca.

Funding Information:
Supported by National Cancer Institute grants to NRG Oncology SDMC (1U10 CA180822), NRG Operations (U10CA180868), and U24CA180803 (IROC). Additionally, Canadian Cancer Trials Group (CCTG) participation in this trial is supported through its grant from the US National Cancer Institute of the National Institutes of Health under the award CA180863. Additional programmatic funding support for the CCTG is provided by the Canadian Cancer Society (704970) and the Canada Foundation for Innovation. Funding was also received from AstraZeneca.

Publisher Copyright:
© American Society of Clinical Oncology.

PubMed: MeSH publication types

  • Clinical Trial, Phase III
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial'. Together they form a unique fingerprint.

Cite this