Comparing durvalumab, olaparib, and cediranib monotherapy, combination therapy, or chemotherapy in patients with platinum-resistant ovarian cancer with prior bevacizumab: the phase II NRG-GY023 trial
Mené sur 153 patientes atteintes d'un cancer épithélial de l'ovaire résistant aux sels de platine, cet essai de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du durvalumab, de l'olaparib et du cédiranib, en monothérapie ou en combinaison, et d'une chimiothérapie standard après l'échec d'un traitement par bévacizumab
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,
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=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.
Clinical Cancer Research , résumé 2024