2022-RA-941-ESGO CEBOC, a single-arm phase II trial to evaluate the safety of cediranib in the prevention of bowel perforation in platinum resistant ovarian cancer

Abstract

2022-RA-939-ESGO Figure 1 Relative mRNA expression of HO-1, IL-1b, IL-4, IL-6, PD-1, PD-L1 genes in PBMCs from ovarian cancer patients on the 1st, 3rd and 5th day after surgery compared to the expression before the treatment. Bar graphs show median value and interquartile range *p<0.05 Results Median age of controls and cancer patients were 59 (26) and 58 (14) years respectively (p>0.05). The mRNA expression of all markers in PBMCs were significantly downregulated in cancer patients before surgery comparing to controls (p<0.05). Relative median expression of HO-1, IL1b, IL-4, IL-6, PD-1 and PD-L1 in controls and cancer patients respectively were 0.97 (0.33) vs 0.66 (0.5), 0.87 (1.95) vs 0.07 (0.16), 0.86 (1.39) vs 0.43 (0.61), 0.98 (1.15) vs 0.03 (0.03), 0.99 (0.94) vs 0.32 (0.50), 1.18 (0.66) vs 0.26 (0.36). Significant post-surgical changes in IL-6 and PD-L1 expression were observed along with not significant fluctuations of other targets expression (figure 1). Conclusion Investigated components of anticancer immunity and immunosuppression mechanisms are affected by cancer and surgical treatment. Therefore, PBMCs are worthy targets for detailed investigation in this field. 2022-RA-941-ESGO CEBOC, A SINGLE-ARM PHASE II TRIAL TO EVALUATE THE SAFETY OF CEDIRANIB IN THE PREVENTION OF BOWEL PERFORATION IN PLATINUM RESISTANT OVARIAN CANCER Alexander Murphy, Catharine Porter, Ann White, Alys Irving, Ruby Ray, Angela Casbard, Tracie-Ann Madden, Reem Mahmood, Robert Morgan, Julia Pugh, Chelsey Wheeler, Victoria Roberts, Giorgio Arnetoli, Zena Salih, Jurjees Hasan, Claire Mitchell, Andrew Clamp, Gordon Jayson. The Christie NHS Foundation Trust, Manchester, UK; Centre for Trials Research, Cardiff University, Cardiff, UK 10.1136/ijgc-2022-ESGO.599 Introduction/Background Systemic treatment of platinum-resistant advanced ovarian cancers (PROC) utilises cytotoxic chemotherapy and vascular endothelial growth factor receptor (VEGFR) inhibitors. However, patients at risk for malignant bowel obstruction (MBO) are excluded from this efficacious combination due to risk of bowel perforation. Methodology We conducted a Simon’s two-stage trial combining oral VEGFR inhibitor cediranib (20 mg/day) with weekly paclitaxel (70 mg/m), in participants with recurrent PROC and clinical and/or radiological features indicating an increased risk of developing MBO. Primary endpoint was number of patients free of grade 3–5 gastrointestinal perforation (GIP) or fistula, from those who received 5 days and £18 weeks cediranib, causally related to cediranib. With 90% power and 5% significance, 24 evaluable patients were required, with 22 free of GIP or fistula to demonstrate safety. Cediranib could start with chemotherapy, or at cycle 2 or 3, once bowel symptoms were CTCAE grade £2. Previous bevacizumab exposure and prior MBO were permitted. Patients were continued on cediranib maintenance after paclitaxel completion, and optionally proceeded to cediranib plus olaparib (300 mg bd) at disease progression. Results 30 participants were enrolled from March 2018 to February 2021. 90% ECOG 0–1, 97% had symptoms showing risk of bowel obstruction. 1 patient died before any treatment. 12 received paclitaxel only (bowel symptoms didn’t improve or deterioration) and subsequently progressed. 17 patients were evaluable for primary endpoint; none developed GIP or fistula. Three cediranib+paclitaxel participants developed bowel obstruction (any grade; including one receiving cediranib+olaparib). Three participants had grade 3+ SAEs causally related to cediranib+/-olaparib (one diarrhoea; one diarrhoea and TIA; one vomiting). Median progression-free survival was 5.4 months (95%CI: 4.18–8.25), and overall survival 15.2 months (95%CI: 8.52–20.5). Abstracts Int J Gynecol Cancer 2022;32(Suppl 2):A1–A504 A281 on D ecem er 2, 2022 by gest. P rocted by coright. http/ijgc.bm jcom / nt J G ynecol C acer: frst pulished as 10.11ijgc-2022-E S G O .99 on 20 O cber 222. D ow nladed fom Abstract 2022-RA-941-ESGO Figure 12022-RA-941-ESGO Figure 1 Conclusion There is no evidence that combining cediranib and taxane chemotherapy is associated with serious toxicity or of developing GIP/fistula, although this is underpowered due to participant withdrawal. 2022-RA-944-ESGO REAL-WORLD SAFETY, BASELINE CHARACTERISTICS AND FIRST-YEAR THERAPY MANAGEMENT IN PATIENTS WITH BRCA1/BRCA2-MUTATED ADVANCED OVARIAN CANCER TREATED WITH OLAPARIB TABLETS IN THE FIRST-LINE MAINTENANCE SETTING: FIRST ANALYSIS OF THE PAN-EUROPEAN OVAL-1 STUDY Domenica Lorusso, Charlie Gourley, Delphine Garbay, Bernard Jean Roger Asselain, Francesco Raspagliesi, Claudio Zamagni, Alexandra Leary, Charlotte Bellier, Ros Glasspool, Gordon Jayson, Angela Whittle, Ilaria Sabatucci, Emmanuelle Grevat, Muriel Licour, Rowan Miller. Dipartimento scienze della salute della donna, del bambino e di sanita’ pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy; Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh, UK; Clinique Tivoli Ducos, Bordeaux, France; ARCAGY-GINECO, Paris, France; Department Of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy; IRCCS Azienda Ospedaliero-universitaria di Bologna, Bologna, Italy; Institut Gustave-Roussy, Villejuif, France; Départements De Cancérologie Gynécologique Et Sénologique, Centre Oscar Lambret, Lille, France; Beatson West of Scotland Cancer Centre and Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; Department of Medical Oncology, The Christie NHS Foundation Trust and Division of Cancer Sciences, Manchester, UK; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Medical Affairs Department, AstraZeneca, London, UK; AstraZeneca, Milan, Italy; AstraZeneca, Paris, France; University College London Hospital, London, UK; St Bartholomew’s Hospital, London, UK 10.1136/ijgc-2022-ESGO.600 Introduction/Background In this preliminary evaluation of the first 324 patients enrolled in the OVAL-1 study (NCT04532645), we report real-world characteristics and firstyear therapy management among tumour or germline (t/g) BRCA1/BRCA2-mutated (t/gBRCAm) newly diagnosed advanced ovarian cancer (OC) patients who received maintenance olaparib across Italy, UK and France. Abstract 2022-RA-944-ESGO Table 1 Baseline characteristics2022-RA-944-ESGO Table 1 Baseline characteristics Abstract 2022-RA-944-ESGO Table 2 AEs2022-RA-944-ESGO Table 2 AEs Methodology This observational, retrospective study included patients who received maintenance olaparib (300 mg bid) for t/gBRCAm advanced OC following response to first-line platinum-based chemotherapy. Eligible patients received their first dose between January 2019 and June 2020 (index date). The planned enrolment is 350 patients. Data are collected from routine clinical practice. Adverse events (AEs) were defined as Abstracts A282 Int J Gynecol Cancer 2022;32(Suppl 2):A1–A504 on D ecem er 2, 2022 by gest. P rocted by coright. http/ijgc.bm jcom / nt J G ynecol C acer: frst pulished as 10.11ijgc-2022-E S G O .99 on 20 O cber 222. D ow nladed fom