Abstract B022: Treatment stratification of targeted therapy in patients with recurrent ovarian cancer by signal transduction pathway activity profiling: the prospective STAPOVER study

Abstract Introduction: Despite advancements in treatment options such as PARP inhibitors and HIPEC, the survival rates for the majority of the ovarian cancer patients remain dismal (Kurnit et al. 2021). Therefore, there is an urgent need for alternative treatment options. Our previous research demonstrated that the Hedgehog and PI3K signal transduction pathways (STPs) serve as oncogenic drivers in late-stage high grade serous cancer (van der Ploeg et al. 2022). Selecting patients for targeted therapy based on high STP activity might improve survival. To investigate this further, the prospective STAPOVER study aims to evaluate the effectiveness of targeted therapy selection in recurrent ovarian cancer patients based on aberrant activated STPs. Methods: Women with recurrent ovarian cancer who have either platinum resistant disease, refrain from standard therapy or are asymptomatic and not yet eligible for palliative chemotherapy, can be enrolled in this study. The OncoSIGNal qPCR test (InnoSIGN) will be employed to assess STP activity of a tumor biopsy sample. High pathway activity in a tumor sample was defined as pathway activity value above the 95% confidence interval (mean+2SD) of reference normal epithelial ovarian tissue (fallopian tube epithelium). Tumors with high Hedgehog and/or PI3K pathway activity will be treated with itraconazole, while tumors demonstrating high estrogen or androgen receptor pathway activity will be treated with letrozole or bicalutamide, respectively. The treatment on basis of active STP is deemed successful when the progression free survival (PFS) under targeted treatment (PFS2) is equal to or longer than the PFS during the preceding treatment (PFS1). Clinical response will be assessed every 12 weeks by RECIST 1. 1 for the duration of clinical benefit. Targeted therapy will be ceased when progression of disease is established. Additionally, every 12 weeks a questionnaire will be send out to evaluate side effects and quality of life. Eventually, cost-effectiveness will be calculated. Results: Since February 2023 (ethical approval August 30, 2021), 6 patients were screened using OncoSIGNal. A total of 5 patients were eligible to enroll based on a high Hedgehog (4) or high Hedgehog+PI3K (1) pathway activity. So far, 4 patients started treatment with itraconazole, the respectively matched targeted therapy. Enrollment and follow-up are ongoing to further assess the clinical responses. Conclusion and next steps: It is feasible to use the OncoSIGNal test for targeted treatment stratification based on signal transduction pathway activity profiles in patients with recurrent ovarian cancer. The evaluation of therapy success is ongoing and first clinical response data are expected Q4 2023. Citation Format: Cynthia S. E. Hendrikse, Phyllis van der Ploeg, Jurgen M. J. Piek. Treatment stratification of targeted therapy in patients with recurrent ovarian cancer by signal transduction pathway activity profiling: the prospective STAPOVER study abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr B022.