Abstract / Summary
Objective The ex vivo functional RAD51 assay (RECAP test) was developed to assess homologous recombination (HR) functionality in viable tumor tissue. This feasibility study aimed to evaluate whether the RECAP test predicts overall response rate to olaparib in patients with recurrent epithelial ovarian cancer. Additionally, circulating tumor DNA was explored as a prognostic biomarker. Methods Twenty-seven patients with recurrent epithelial ovarian cancer and disease progression at least three months after the last platinum-based chemotherapy were included. All patients received olaparib. Tumor biopsies were obtained prior to treatment initiation, blood samples were collected at baseline, after two treatment cycles, and at disease progression. HR status was determined using the RECAP test, while ctDNA was assessed using mFastSeq. The primary aim was to determine whether the RECAP test correlates with objective response rate, secondary endpoints were progression-free survival and overall survival. Results The RECAP test was successfully performed in 10 out of 24 tumor biopsies (42%). Of these, six tumors (60%) were classified as HR-proficient (HRP), three (30%) as HR-intermediate (HRI), and one (10%) as HR-deficient (HRD). Given the limited number of informative biopsies and the identification of only one HRD tumor in our cohort, evaluation of the primary endpoint and HR subgroup analyses was not feasible. Elevated ctDNA levels at baseline and after two treatment cycles were associated with shorter progression-free survival and overall survival (p=0.014,p=0.048, Cox-regression). Conclusions Functional HRD assessment using the RECAP test demonstrated limited feasibility in patients with recurrent epithelial ovarian cancer, precluding evaluation of its predictive value for response to olaparib. Exploratory analyses suggest that ctDNA levels may be associated with clinical outcomes in patients treated with olaparib.