Next generation sequencing in ovarian cancer patients: Does personalized medicine improve oncological outcomes?

Abstract

5553 Background: Ovarian cancer (OC) is the second most common gynecologic malignancy and the most common cause of gynecologic cancer mortality in the United States. Homologous recombination deficiency (HRD), including the BRCA mutations, are found in 50% of OC tumors. Next generation sequencing (NGS) provides understanding the underlying molecular and genetic patterns to improve OC treatment. This study examines the prognostic and predictive biomarkers identified with NGS in hopes to improve OC patients outcomes. Methods: The patient cohort included 890 consecutive OC patients treated between 2002 and 2020,at the Tel-Aviv Medical Center. We retrospectively evaluated patients with histopathologically confirmed OC. Cox models were used to analyze the clinical impact of various mutations and biomarkers among OC patients with and without FoundationOne CDx NGS testing, by assessing overall survival (OS), progression free survival (PFS), and physicians' timing preferences for referral to NGS testing. Results: Among the 890 OC patients, 103 (11.57%) completed NGS molecular testing. The median OS among patients with and without NGS testing, adjusted for age, stage and recurrence status, was 73.36 and 68.50 months, respectively (P =.02). The median PFS was 17.23 and 17.43 months, respectively (P =.77). We also evaluated physicians' preferences regarding timing of molecular profiling, upon diagnosis, after first recurrence and at advanced line of treatment in 31.95%, 36.08% and 26.8% of practitioners, respectively. Of the patients who completed NGS, 48 (52.75%) harbored actionable mutations, and 21 patients (43.75%) received matched targeted therapy. Forty-five patients were microsatellite stable (MSS) (45%), 55 with undetermined status (55%) and 0 patients with MSI-H. Forty-one (71.93%) patients had low ( < 5) tumor mutation burden status (TMB), 16 (28.07%) intermediate (5-15) and none with high ( > 15) TMB. There was no noticeable survival difference when comparing low with intermediate TMB (P = 0.3). Loss of heterozygosity (LOH) was a significant prognostic biomarker. Patients with high LOH (hLOH > = 16%) had longer OS compared to low LOH (lLOH < 16%), 99.02 vs. 50.23 months, respectively (P <.005). Patients with hLOH and BRCA mutations (BRCA+) had longer OS compared to hLOH/BRCA WT (BRCA-), lLOH/BRCA+, and lLOH/BRCA-, with an unreached median OS of 91.5 vs. 60.48 vs. 45.21 months, respectively (P =.005). Conclusions: Our work demonstrates the clinical benefit of NGS personalized medicine as a cornerstone of future treatment strategies in OC. Our study suggests an OS benefit among the NGS tested cohort. We identified LOH as a prognostic biomarker. Prospective studies evaluating larger cohorts are necessary to generate a more extensive evaluation of additional prognostic and predictive biomarkers among OC patients.