Objective The ex vivo functional RAD51 assay (REcombination CAPacity test) was developed to assess homologous recombination functionality in viable tumor tissue. This feasibility study aimed to evaluate whether the REcombination CAPacity test predicts the overall response rate to olaparib in patients with recurrent epithelial ovarian cancer. Additionally, circulating tumor deoxyribonucleic acid (DNA) was explored as a prognostic biomarker. Methods Twenty-seven patients with recurrent epithelial ovarian cancer and disease progression at least 3 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 2 treatment cycles, and at disease progression. Homologous recombination status was determined using the REcombination CAPacity test, while circulating tumor DNA was assessed using mFastSeq. The primary aim was to determine whether the REcombination CAPacity test correlates with objective response rate; secondary endpoints were progression-free survival and overall survival. Results The REcombination CAPacity test was successfully performed in 10 out of 24 tumor biopsies (42%). Of these, 6 tumors (60%) were classified as homologous recombination-proficient, 3 (30%) as homologous recombination-intermediate, and 1 (10%) as homologous recombination-deficient. Given the limited number of informative biopsies and the identification of only 1 homologous recombination-deficient tumor in our cohort, evaluation of the primary endpoint and homologous recombination sub-group analyses was not feasible. Elevated circulating tumor DNA levels at baseline and after 2 treatment cycles were associated with shorter progression-free survival and overall survival (p=.014, p=.048, Cox-regression). Conclusions Functional homologous recombination-deficient assessment using the REcombination CAPacity 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 circulating tumor DNA levels may be associated with clinical outcomes in patients treated with olaparib.
