Olaparib alone or in combination with cediranib failed to improve progression-free survival (PFS), compared with platinum chemotherapy, in a phase 3 trial of patients with recurrent, platinum-sensitive ovarian cancer.

Despite the lack of improvement in the overall cohort, olaparib monotherapy and olaparib-cediranib did exhibit activity in a subset of patients with a germline BRCA mutation. These results were published in the Journal of Clinical Oncology.

In the phase 3 NRG-GY004 trial (ClinicalTrials.gov Identifier: NCT02446600), researchers sought to determine whether 2 oral regimens, olaparib-cediranib and olaparib monotherapy, can improve PFS compared with standard platinum-based chemotherapy in patients with high-grade serous or endometrioid platinum-sensitive ovarian cancer.


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The trial enrolled 565 patients in the United States and Canada. The participants were randomly assigned 1:1:1 to platinum-based chemotherapy (187 patients), olaparib alone (189 patients), or olaparib-cediranib combination therapy (189 patients).

Baseline characteristics were well balanced across the treatment arms. Overall, about 65% of patients had received 1 previous therapy, fewer than 10% had received previous antiangiogenic therapy, and nearly 25% had a deleterious germline BRCA1/2 mutation.

The median PFS was 10.3 months in the chemotherapy arm, 8.2 months in the olaparib arm, and 10.4 months in the olaparib-cediranib arm. 

Olaparib-cediranib did not improve PFS compared with chemotherapy (hazard ratio [HR], 0.86; 95% CI, 0.66-1.10; P =.077). The researchers did not conduct a formal comparison of PFS between olaparib monotherapy and chemotherapy, but the HR for olaparib monotherapy was 1.2 (95% CI, 0.93-1.5).

Among patients with a germline BRCA mutation, the HR for PFS was 0.55 (95% CI, 0.32-0.94) for olaparib-cediranib vs chemotherapy and 0.63 (95% CI, 0.37-1.07) for olaparib vs chemotherapy.

Among patients without a germline BRCA mutation, the HR for PFS was 0.97 (95% CI, 0.73- 1.30) for olaparib-cediranib vs chemotherapy and 1.41 (95% CI, 1.07-1.86) for olaparib vs chemotherapy.

Overall survival data were not mature at the time of analysis, but there were no significant differences between the treatment arms.

Patients receiving chemotherapy had more frequent hematologic adverse events (AEs), but nonhematologic AEs were more common in patients treated with olaparib plus cediranib.

“The observed activity of olaparib/cediranib and olaparib, particularly in patients with BRCA-mutated tumors, warrants further exploration and development of non-platinum-based alternatives, especially in selected patient populations with platinum-sensitive ovarian cancer,” the researchers wrote.

Disclosures: This research was partially supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Liu JF, Brady MF, Matulonis UA, et al. Olaparib with or without cediranib versus platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer (NRG-GY004): A randomized, open-label, phase III trial. J Clin Oncol. Published online March 15, 2022. doi:10.1200/JCO.21.02011