Purpose: We assessed the efficacy of anti-PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared to the standard-of-care chemotherapy (SOC) in platinum-resistant epithelial ovarian cancer (PROC) patients, with prior bevacizumab.
Patients and methods: NRG-GY023 was the first, randomized 4-arm superiority phase II trial enrolling high-grade serous/endometrioid or clear cell PROC patients with prior bevacizumab exposure. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin), DOC, durvalumab+cediranib (DC), or olaparib+cediranib (OC). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. The design had 80% power to detect a hazard ratio (HR) of 0.5 using a one-sided, ⍺=0.1 level test for each comparison to the SOC with a pre-planned interim analysis. Experimental arms with HR estimate (vs SOC)>0.87 could be discontinued.
Results: 153 patients were enrolled between 4/28/2021, and 2/1/2023. Accrual was permanently closed on 2/1/2023, due to futility. With a data cut-off of 9/9/2024, the median PFS was 3.4, 2.9, 2.5 and 2.8 months, and median OS was 7.5, 8.3, 5.7 and 10.2 months for SOC, DOC, DC and OC, respectively. ORR was 4.3%(95%CI:0.00-0.19), 15.9%(95%CI:0.07-0.29), 11.9%(95%CI:0.05-0.24) and 9.1%(95%CI:0.03-0.20) for SOC, DOC, DC, OC. Compared to SOC, the PFS HR estimates for DOC, DC, OC were 1.003(95%CI:0.56-1.80), 1.108(95%CI:0.63-1.96), and 1.021(95%CI:0.57-1.82). for SOC, DOC, DC, OC, respectively. No new safety signals were observed.
Conclusion: In PROC patients with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.