Abstract 942: Response to systemic therapies in patient-derived cell lines from primary and recurrent adult granulosa cell tumors

Abstract Introduction: In patients with adult-type granulosa cell tumor (aGCT), a rare subtype of ovarian cancer, surgery is the preferred treatment for both primary and recurrent disease. However, the probability of complete resection decreases after multiple recurrences, in which case systemic treatment is an alternative option. Response rates of systemic therapy are variable, resistance is a problem and it is difficult to predict which therapy will work in which patient. Drug screen testing on patient-derived aGCT cell lines may offer a solution. Methods: In a national prospective study on aGCT, fresh tissue was collected immediately after surgery. Tumor tissue was cultured and developed into 2D cell lines. Both clinically applicable and experimental drugs were tested on the patient-derived cell lines and two control cell lines. Dose-response curves and synergy were calculated using GraphPad Prism and Compusyn software. Results: We cultured 34 patient-derived cell lines from tissue of seven patients with primary aGCT and from 13 patients with recurrence. In eight patients multiple sites were cultured. A total of 27 drugs were tested, including 10 monotherapies and 17 combinations. Carboplatin/gemcitabine showed efficacy and synergy 33 of 34 patient-derived cell lines (97%), in contrast to the regular carboplatin/paclitaxel and carboplatin/etoposide combinations (50% and 74%, respectively). The experimental combinations alpelisib/fulvestrant and alpelisib/gemcitabine showed efficacy of more than 75%. Testing of anti-hormonal therapy was not sufficiently reliable with this technique. Conclusion: Drug screening on patient-derived tumor cell lines adequately reflects the reality of the variable response to systemic therapy in aGCT. In future research, this technique could be used to personalize the systemic treatment of aGCT patients. The response to carboplatin/gemcitabine in our patient-derived cell lines is striking. Citation Format: Geertruid Brink, Nizar Hami, Sander Mertens, Ward Hofhuis, Jurgen Piek, Cor de Kroon, Christianne Lok, Eva Maria Roes, Luc van Lonkhuijzen, Hans Nijman, Hugo Snippert, Jolijn Groeneweg, Petronella Witteveen, Ronald Zweemer. Response to systemic therapies in patient-derived cell lines from primary and recurrent adult granulosa cell tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 942.