Threshold of tumor mutational burden and association with survival in ovarian cancer (172)

Abstract

<b>Objectives:</b> Targeted therapies based on molecular profiling have been integrated into treatment guidelines for patients with ovarian cancer. Recently, the FDA approved pembrolizumab for patients with tumor mutational burden-high (TMB-H) (≥10 mutations/megabase [mut/Mb]) solid tumors. However, trials evaluating checkpoint inhibitors in patients with ovarian cancer have had limited efficacy. We characterized patients with ovarian cancer who had undergone next-generation sequencing to characterize the landscape tumor mutational burden by histologic subtype and clinical outcome. <b>Methods:</b> A retrospective cohort study was performed on patients diagnosed with ovarian cancer who underwent Foundation One testing between 2015 and 2021 at a single academic institution. Demographic and clinical characteristics were abstracted, including age, race/ethnicity, stage, histology, and follow-up time in months. Kaplan-Meier curves and Cox regression analyses were used to estimate overall survival (OS) and progression-free survival (PFS). <b>Results:</b> We identified 128 patients diagnosed with ovarian cancer and underwent Foundation One testing. Most patients (51, 39.8%) had high-grade serous histology. Other histologies included 24 (18.8%) low-grade serous, 20 (15.6%) clear cell, five (3.9%) mucinous, five (3.9%) endometrioid, one germ cell (0.8%), six sex cord-stromal (4.7%), 11 carcinosarcoma (8.6%), three adenocarcinomas not otherwise classified (2.3%), and two (1.6%) borderline tumors. The median age at diagnosis was 62 years (range: 18-78 years). TMB was available for 93/128 patients. Most patients (83, 89.2%) had low TMB defined as 0-5 mut/Mb. Ten patients (10.8%) had intermediate TMB defined as 6-19 mut/Mb. Tumors from patients with TMB ≤5 mut/Mb had significantly longer PFS (p=0.005) but not OS (p=0.55) than those with TMB > 5 mut/Mb. Eighty (62.5%) patients developed recurrent ovarian cancer. Of those who developed recurrent disease, there was a significant difference in PFS (p=0.02) but not OS (p=0.58) when comparing TMB ≤5 versus > 5. <b>Conclusions:</b> In an era of biomarker-driven care, TMB may be a useful adjunctive prognostic tool for patients with ovarian cancer. Future work should evaluate how TMB predicts response and benefit to immunotherapy.