Abstract PO025: Development of patient derived organoid cultures of two advanced stage serous carcinomas of the uterus

Abstract

Abstract Advanced stage serous carcinoma of the uterus typically portends a poor prognosis. There is an urgent need to augment clinical trial data with different methods of treatment evaluation before a patient is made to try and potentially fail a therapy. Patient derived organoids (PDOs) may represent such an opportunity. We describe the successful culture and drug sensitivity testing of two PDOs from patients with advanced stage serous carcinoma of the uterus who received neoadjuvant chemotherapy. Clinical response to treatment was compared with the organoid response to the same regimens. Drug sensitivity data are reported as percentage of residual cell viability 48 hours after one standard treatment dose, in which 100% viability indicates no response and 0% viability reflects complete cell death. We hypothesized that significant cell killing, i.e. a low cell viability in our assay, would be required to achieve clinical drug sensitivity in patients. Both patients were clinically platinum resistant. Patient 1 had a large burden of disease at the time of presentation, including skeletal and liver metastasis. Though she initially partially responded to triplet therapy of paclitaxel, carboplatin and bevacizumab, she ultimately had persistent unresectable disease after 6 cycles of therapy. The percent residual, post-drug cell viability for PDO-1 was 45% in response to paclitaxel, carboplatin and bevacizumab combinatorial treatment, 35% in response to paclitaxel and carboplatin, and 100% in response to single agent bevacizumab. Patient 2 received paclitaxel, carboplatin and trastuzumab because her tumor was positive for HER2neu. Though she also had an initial response to treatment, she experienced a recurrent malignant pleural effusion 3 months after completing platinum-containing triplet (trastuzumab was continued as a maintenance therapy). The percent residual cell viability for PDO-2 was 51% in response to the combination of paclitaxel and carboplatin. Previous investigators have identified PDOs as a potentially powerful functional model for treatment response. We confirm that it is feasible to establish organoids and to rapidly test agents for cell sensitivity even prior to the first post-surgical chemotherapeutic treatment cycle. For both patients, the PDO models were only moderately sensitive to the agents used for therapy, and the lack of long-term benefit achieved for these patients may have been suggested a priori by the PDO models. However, further studies are necessary to establish a threshold percent value of post-treatment cell viability that is predictive of clinical patient response. We hypothesize that such a threshold appears to be significantly below 50% from these two initial cases. Citation Format: Andreea M. Newtson, Jianling Bi, Yuping Zhang, Eric Devor, Kristina Thiel, Kimberly K. Leslie. Development of patient derived organoid cultures of two advanced stage serous carcinomas of the uterus [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO025.