Results of the NRG Oncology phase III clinical trial NRG-GY004 indicated that the addition of the investigational agent cediranib to olaparib and standard platinum-based chemotherapy did not improve progression-free survival outcomes for women with platinum-sensitive ovarian cancer; however, activity between the treatments was similar in patients. These results were presented by Joyce F. Liu, MD, MPH, of the Dana-Farber Cancer Institute, Boston, and colleagues during the ASCO20 Virtual Scientific Program.1
Study Background and Methodology
NRG-GY004 was designed to expand upon the findings of a phase II trial that indicated a combination of cediranib and olaparib improved progression-free survival outcomes compared with olaparib alone for women with platinum-sensitive, high-grade serous/endometrioid ovarian cancer, regardless of whether they had a BRCA mutation.
Joyce F. Liu, MD, MPH
In NRG-GY004, women were randomly assigned to one of three treatment regimens. Participants in the first treatment arm received standard-of-care chemotherapy with either carboplatin and paclitaxel, carboplatin and gemcitabine, or carboplatin and pegylated lipsomal doxorubicin. Participants on the experimental treatment arms received either olaparib at 300 mg twice a day or olaparib at 200 mg twice a day with cediranib at 30 mg twice a day. The primary endpoint was to assess the progression-free survival benefit of cediranib and olaparib compared with chemotherapy in platinum-sensitive ovarian cancer.
Between March 2016 and June 2018, 565 patients had enrolled in NRG-GY004 and, of those patients, 528 initiated treatment A total of 23.7% of the patients had a germline BRCA mutation.
At a median follow-up of 29.1 months, the hazard ratio for progression-free survival was 0.856 (P = .08) for the combination of cediranib and olaparib compared with chemotherapy treatment. The hazard ratio for progression-free survival was 1.20 (95% CI = 0.93–1.54) for olaparib alone compared with chemotherapy treatment. Median progression-free survival for patients was 10.3 months for the standard of care chemotherapy; 8.2 months for olaparib alone; and 10.4 months for patients receiving cediranib plus olaparib. In a predefined biomarker subset analysis of women with a germline BRCA mutation, the progression-free survival hazard ratio was 0.55 (95% CI = 0.73–1.30) for combined cediranib and olaparib compared with chemotherapy and 0.63 (95% CI = 0.37–1.07) for olaparib alone vs standard chemotherapy. In women without a germline BRCA mutation, the progression-free survival hazard ratio was 0.97 (95% CI = 0.73–1.30) for cediranib plus olaparib compared with chemotherapy and 1.41 (95% CI = 1.07–1.86) for olaparib alone vs standard chemotherapy.
There were no overall survival differences between the treatment arms. Patients who received cediranib and olaparib in addition to the standard of care did experience a higher frequency of grade 3 or higher gastrointestinal adverse events, hypertension, and fatigue.
Disclosure: Dr. Liu has served as a consultant or advisor to Clovis Oncology, Genentech/Roche, GlaxoSmithKline, Mersana, Tesaro, and Regeneron; has received institutional research funding from 2X Oncology, Acetylon, Agenus, Aravive, Arch Oncology, AstraZeneca, Atara Biotherapeutics, Boston Biomedical, Bristol Myers Squibb, Clovis Oncology, CytomX Therapeutics, Genentech/Roche, Regeneron, Surface Oncology, Tesaro, and Vigeo Therapeutics; and has been reimbursed for travel, accommodations, or expenses by AstraZeneca and Merck.
1. Liu JF, Brady MF, Matulonis, UA, et al: ASCO20 Virtual Scientific Program. Abstract 6003.