Results of a randomised Phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer

Abstract

Background OCTOVA compared the efficacy of olaparib (O) versus weekly paclitaxel (wP) or olaparib + cediranib (O + C) in recurrent ovarian cancer (OC). Aims The main aim of the OCTOVA trial was to determine the progression-free survival (PFS) of olaparib (O) versus the oral combination of olaparib plus cediranib (O + C) and weekly paclitaxel (wP) in recurrent ovarian cancer (OC). Methods In total, 139 participants who had relapsed within 12 months of platinum therapy were randomised to O (300 mg twice daily), wP (80 mg/m2 d1,8,15, q28) or O + C (300 mg twice daily/20 mg daily, respectively). The primary endpoint was progression-free survival (PFS) of olaparib (O) versus olaparib plus cediranib (O + C) or weekly paclitaxel (wP). The sample size was calculated to observe a PFS hazard ratio (HR) 0.64 in favour of O + C compared to O (20% one-sided type I error, 80% power). Results The majority had platinum-resistant disease (90%), 22% prior PARPi, 34% prior anti-angiogenic therapy, 30% germline BRCA1/2 mutations. The PFS was increased for O + C vs O (O + C 5.4 mo (2.3, 9.6): O 3.7 mo (1.8, 7.6) HR = 0.73; 60% CI: 0.59, 0.89; P = 0.1) and no different between wP and O (wP 3.9 m (1.9, 9.1); O 3.7 mo (1.8, 7.6) HR = 0.89, 60% CI: 0.72, 1.09; P = 0.69). The main treatment-related adverse events included manageable diarrhoea (4% Grade 3) and hypertension (4% Grade 3) in the O + C arm. Discussion OCTOVA demonstrated the activity of O + C in women with recurrent disease, offering a potential non-chemotherapy option. Trial registration ISRCTN14784018, registered on 19th January 2018 http://www.isrctn.com/ISRCTN14784018.

Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials

“…Upon detailed examination, 51 studies were deemed unfit for inclusion: 5 were single-arm clinical trials; 2 were non-comparative clinical studies; 3 trials included duplicate patient data; 23 trials exhibited intervention and control designs that did not align with the inclusion criteria; and 18 articles failed to report the necessary outcome data. Finally, 35 RCTs were selected for inclusion in the meta-analysis ( Aghajanian et al, 2012 ; Aghajanian et al, 2015 ; Burger et al, 2011 ; Chekerov et al, 2018 ; Coleman et al, 2017 ; du Bois et al, 2014 ; du Bois et al, 2016 ; Duska et al, 2020 ; Ferron et al, 2023 ; Gore et al, 2019 ; Gotlieb et al, 2012 ; Hall et al, 2020 ; Herzog et al, 2013 ; Karlan et al, 2012 ; Kim et al, 2018 ; Ledermann et al, 2021 ; Ledermann et al, 2016 ; Ledermann et al, 2011 ; Liu et al, 2019 ; Liu et al, 2022 ; Marth et al, 2017 ; Monk et al, 2016b ; Nicum et al, 2024 ; Oza et al, 2015 ; Pignata et al, 2021 ; Pignata et al, 2015 ; Pujade-Lauraine et al, 2014 ; Ray-Coquard et al, 2020 ; Richardson et al, 2018 ; Roque et al, 2022 ; Shoji et al, 2022 ; Tewari et al, 2019 ; Vergote et al, 2019a ; Vergote et al, 2019b ; Wang et al, 2022 ) ( Figure 1 ).…”

“…However, there is a lack of a comprehensive meta-analysis to evaluate the effects of monotherapy or combination therapy with anti-angiogenic drugs on OC. Moreover, multiple RCTs have published the latest relevant clinical results in recent years ( Liu et al, 2022 ; Roque et al, 2022 ; Ferron et al, 2023 ; Nicum et al, 2024 ). Therefore, we conducted a meta-analysis to systematically assess the efficacy and safety of anti-angiogenic drug monotherapy or combined with chemotherapy or PARP inhibitors in the treatment of OC.…”

Uncovering miRNA–mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors

“…Over recent years novel olaparib combinations have been evaluated to combat associated resistance and improve outcomes in OC patients. For instance, the addition of some agents, including antiangiogenic molecules or the ATR/CHK1 pathway inhibitors, has shown beneficial antitumor effects clinically in OC [5,6]. The ATR/CHK1 pathway is involved in multiple aspects of the DNA damage response, including the activation of cell cycle checkpoints, the stabilization of stalled replication forks, and the regulation of DNA repair pathways [7,8].…”