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 recently presented by Joyce F. Liu, MD, and colleagues during the ASCO20 Virtual Scientific Program (Abstract 6003).
Joyce F. Liu, MD
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 to olaparib alone for women with platinum-sensitive, high-grade serous/endometrioid ovarian cancer, regardless if they had a BRCA mutation.
In NRG-GY004, women were randomly assigned to one of three treatment regimens. Participants randomly assigned to the first treatment arm received standard-of-care chemotherapy with either carboplatin and paclitaxel, carboplatin and gemcitabine, or carboplatin and pegylated lipsomal doxorubicin. The participants on the experimental treatment arms either received 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 of this study was to assess the progression-free survival benefit of cediranib and olaparib treatment compared to chemotherapy for women with platinum-sensitive ovarian cancer.
Between March 2016 and June 2018, 565 patients had enrolled in NRG-GY004 and, of those patients, 528 initiated treatment; 23.7% of the patients had a germline BRCA mutation.
Results
At a median follow-up of 29.1 months, the hazard ratio for progression-free survival was 0.856 (95% confidence interval [CI] = 0.66–1.11, P = .08, 1-tail) for the combination of cediranib and olaparib compared to chemotherapy treatment. The hazard ratio for progression-free survival was 1.20 (95% CI = 0.93–1.54) for olaparib alone compared to 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 to 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 to chemotherapy and 1.41 (95% CI = 1.07–1.86) for olaparib alone vs standard chemotherapy.
"While the combination of cediranib and olaparib was not found to improve progression-free survival compared to [the] standard-of-care chemotherapy, the findings of this study suggest that non–platinum-based alternatives have potential in this setting, especially in appropriate biomarker subgroups such as patients with BRCA mutations."— Joyce F. Liu, MD
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“This is the first phase III trial comparing a completely oral non–platinum-based therapy regimen to standard of care platinum-based chemotherapy in platinum-sensitive ovarian cancer. While the combination of cediranib and olaparib was not found to improve progression-free survival compared to [the] standard-of-care chemotherapy, the findings of this study suggest that non–platinum-based alternatives have potential in this setting, especially in appropriate biomarker subgroups such as patients with BRCA mutations,” stated Dr. Liu, of the Dana-Farber Cancer Institute.
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, hypertension, and fatigue adverse events.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
