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 (PFS) outcomes for women with platinum-sensitive ovarian cancer; however, activity between the treatments was similar in patients.
These results were recently presented at the virtual Annual Meeting of the American Society of Clinical Oncology (ASCO).
NRG-GY004 was designed to expand upon the findings of a phase II trial that indicated a combination of cediranib and olaparib improved PFS outcomes compared to olaparib alone for women with platinum-sensitive, high-grade serous/endometrioid ovarian cancer, regardless if they had a BRCA mutation. On NRG-GY004, women were randomly assigned to one of three treatment regimens.
Participants randomly assigned to the first treatment arm received the standard of care chemotherapy with either carboplatin and paclitaxel, carboplatin and gemcitabine, or carboplatin and pegylated liposomal doxorubicin.
The participants on the experimental treatment arms either received olaparib at 300mg twice a day or olaparib at 200mg twice a day with cediranib at 30mg twice a day.
The primary endpoint of this study was to assess PFS 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.
At a median follow-up of 29.1 months, the hazard ratio for PFS was 0.856 (95% CI 0.66-1.11, p = 0.08, 1-tail) for the combination of cediranib and olaparib compared to chemotherapy treatment.
The hazard ratio for PFS was 1.20 (95% CI 0.93-1.54) for olaparib alone compared to chemotherapy treatment.
Median PFS 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 combination cediranib and olaparib.
In a predefined biomarker subset analysis of women with a germline BRCA mutation, the PFS 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 versus the standard chemotherapy.
In women without a germline BRCA mutation, the PFS hazard ratio was 0.97 (95% CI 0.73-1.30) for combined cediranib and olaparib compared to chemotherapy and 1.41 (1.07-1.86) for olaparib alone versus standard chemotherapy.
This is the first Phase 3 trial comparing a completely oral non-platinum-based therapy regimen to the standard of care platinum-based chemotherapy in platinum-sensitive ovarian cancer. While the combination of cediranib and olaparib was not found to improve PFS compared to standard of care chemotherapy, the findings of this study suggest that non-platinum based alternatives have potential in this setting, especially inappropriate biomarker subgroups such as patients with BRCA mutations."\
Joyce Liu, MD, MPH, Lead Author of the NRG-GY004 Abstract, 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.
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