Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial￼
The study was designed to evaluate the possibility of avoiding chemotherapy in the setting of platinum-sensitive relapsed ovarian cancer. However, chemotherapy was superior to Olaparib/cediranib and Olaparib alone. In addition, cost and duration of therapy of Olaparib-based therapy are likely more and longer respectively as compared to chemotherapy.
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).
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.
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.
Author Affiliations1Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 2NRG Oncology; Clinical Trial Development Division; Biostatistics & Bioinformatics; Roswell Park Comprehensive Cancer Center, Buffalo, NY 3Gynecologic Cancer Therapeutics, National Cancer Institute, Rockville, MD 4Gynecologic Oncology, University of Washington, Seattle, WA 5Department of Medical Social Sciences, Northwestern University Health System, Chicago, IL 6Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 7Texas Oncology, Fort Worth Cancer Center, Fort Worth, TX 8Gynecologic Oncology, University of New Mexico, Albuquerque, NM 9Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 10Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester, Rochester, NY 11Gynecologic Oncology, Cancer Research Consortium of West Michigan, Munson Medical Center, Traverse City, MI 12Gynecologic Oncology, Cleveland Clinic Health System, Cleveland, OH 13Ob/Gyn & Women’s Health, University of Minnesota, Minneapolis, MN 14Gynecologic Oncology, Saitama Medical University International Medical Center; Hidaka-Shi, Japan 15Executive Chair, Sutter Cancer Research Consortium, Sutter Health Research Enterprise, Sacramento, CA 16Kapialoni Medical Center for Women & Children, University of Hawaii, Honolulu, HI 17Gynecologic Oncology, Duke University Medical Center, Durham, NC 18Stephenson Cancer Center Gynecologic Cancers Clinic, University of Oklahoma Health Sciences Center, Oklahoma City, OK 19Director, Gynecologic Oncology Therapeutics, Kaiser Permanente Northern California, San Francisco, CA
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