2nd Edition of Cell & Gene Therapy World Conference 2026

Abstract

Background: In the 2020 national health basket, PARP poly (adenosine diphosphate–ribose) polymerase inhibitor) such as Olaparib were approved in Israel as maintenance therapy for newly diagnosed BRCA mutated ovarian cancer, following the SOLO1 study (October 21, 2018 N Engl J Med 2018; 379:2495-2505). This study demonstrated a significant improvement in progression-free survival (PFS) compared to placebo after surgery and chemotherapy in BRCA mutated women. Although the results were substantial, real-world data studies sometimes yield different outcomes compared to randomized controlled trials. Objectives: To evaluate the effectiveness of Olaparib treatment and compare the findings to the registration trial data. Materials and Methods: This retrospective study included 31 patients with newly diagnosed advanced/metastatic ovarian cancer and a BRCA mutation, between January 2020 and March 2022. PFS, overall survival (OS), oncological response parameters, and clinical variables were assessed. Data were taken from patients' files.  Local  Ethics Committee permission was approved. BRCA mutations detection was done in a central lab in Israel validated by the Israeli Ministry Health. All patients characteristics including ethnicity, disease status and treatment were evaluated. Results: The mean age of the patients was 64 years, with 71% being over 60.  20 patients were performance status 3 (more than 50% of day time in bed). The majority carried a BRCA1 mutation (71%), while others had BRCA2 mutations (16.1%) or a combination of both (3.2%). All patients underwent surgery, chemotherapy, and subsequent maintenance therapy with Olaparib. The median PFS was 43 months, while OS was 46.75 months. The probability of PFS at 24 months was 75.5%, and the probability of OS was 86.8%. Subgroup analysis did not reveal significant differences in PFS or OS based on age, smoking history, disease stage at surgery, mutation type, or neoadjuvant chemotherapy. No significant difference in PFS was found between BRCA1 or BRCA2 mutated patients. Side effects were acceptable. However, a statistical trend suggested a decline in PFS and OS with more extensive disease spread. Conclusion: The use of Olaparib demonstrates effectiveness in patients with advanced/metastatic ovarian cancer carrying a BRCA mutation; however, the outcomes are not as promising as those reported in the registration trial (43 months in this study compared to 56.6 months observed in SOLO1). Future studies are ongoing to detect the effect of ethnicity on PFS.