Abstract 761P
Background
Cisplatin-based chemotherapy remains the perioperative treatment in muscle-invasive bladder carcinoma (MIBC). Current evidence suggests that immune checkpoint inhibitors could be incorporated in this setting. PARP inhibitors have a well-established role in HRD tumors. Results from trials assessing the combination of durvalumab and olaparib suggest a synergistic effect. However, molecular characterization is crucial to warrant a rational development.
Methods
A phase II clinical trial was designed to assess the impact of neoadjuvant treatment with the combination of durvalumab plus olaparib in the molecular profile of MIBC (NCT03534492; SOGUG-2017-A-IECVEJ-2). Efficacy and safety were secondary objectives. Subjects with cT2-T4a MIBC aimed for cystectomy were treated during 6 to 8 weeks pre-cystectomy. Pre and postreatment surgical and blood samples have been collected for the molecular analysis. We present final results regarding efficacy and safety.
Results
From November 2018 to October 2019 29 patients have been enrolled (89.7% males). 58.6%/41.4% of patients had PS 0/1. Median age was 71. Stage was: pT2 in 79,3% patients, pT3 in 13.8%, pT4 in 6.9%; and 13.7% presented nodal spread. 4 tumors had squamous histology. 3 patients had history of NMIBC. Median time on olaparib treatment was 7 weeks; no dose reductions were indicated. 2 patients required early withdrawn of treatment due to sepsis and progressive disease respectively. Combination was well tolerated with 3.4% of grade 3 toxicity (neutropenia) without unexpected adverse events. 89.7% of patients underwent cystectomy. 2 patients suffered grade 3 wound evisceration and 2 patients died due to postoperative complications. Radiological evaluation after neoadjuvant treatment showed 24.1% of partial response, 51.7% stable disease, 10.3% progressive disease and 13.8% not evaluable. From 26 cystectomies, pathological complete response rate is 50%.
Conclusions
Clinical data suggest that combination Durvalumab-Olaparib could be active and well-tolerated as neoadjuvant treatment of MIBC. Molecular characterization and biomarker discovery will be presented separately.
Clinical trial identification
NCT03534492 SOGUG-2017-A-IEC(VEJ)-2.
Editorial acknowledgement
Legal entity responsible for the study
Spanish Oncology Genitourinary Group (SOGUG).
Funding
AstraZeneca.
Disclosure
J.F. Rodriguez-Moreno: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas. All other authors have declared no conflicts of interest.