Abstract A04: Real-world usage of NGS testing in high-grade serous ovarian cancer (HGSOC)—the landscape is quickly changing

Abstract

Abstract Introduction: The Precision Medicine Initiative (PMI) study at the University of Alabama at Birmingham (UAB) was developed to include next-generation sequencing (NGS) as part of patients’ standard of care and to follow them prospectively. The objective of this study was to analyze how the usage of NGS in patients with high-grade serous ovarian cancer (HGSOC) affected their management. Methods: Between 5/2015–2/2019, 224 ovarian cancer patients (167 HGSOC) signed informed consent and were enrolled. Archival tissue was sent to Foundation Medicine for NGS analysis; 324 genes, including genes involved in homologous recombination repair deficiency (HRD genes), microsatellite instability (MSI) status, and tumor mutation burden (TMB) were assessed. A subset of these patients were tested for LOH status and PD-L1 expression. Demographics including germline BRCA status, treatments, duration of targeted therapy, and platinum sensitivity were collected. Correlation between LOH status and both germline and somatic mutations in HRD genes was analyzed, in addition to the correlation between PD-L1 positivity and MSI status and TMB. Results: 62% (103/167) of HGSOC patients had at least 1 targetable mutation and 40 patients received targeted therapy. 16% (27/167) were germline BRCA+ (gBRCAm+), 12 (10%) somatic BRCA + (sBRCAm+), and 120 wtBRCA. Of the gBRCAm+ patients, 81% were platinum sensitive, compared to 66% of all patients. 22% (36/167) of patients underwent LOH testing: 39% (14/36) were LOH-high. 43% (6/14) of LOH-high patients had an alteration in one of the HRD genes. Of the LOH-low patients, 23% (5/22) harbored mutations in HRD genes: (3) BRCA2, (2) CHEK2. 7% (8/114) of platinum-sensitive patients were placed on PARPi maintenance therapy after two or more lines of platinum-based therapy. Of the s/gBRCA+ patients, 24% (11/39) received PARPi monotherapy; 8 received both maintenance PARPi and monotherapy. 33% (13/167) of patients received a non-PARPi targeted therapy based on their NGS testing. Patients on maintenance PARPi received it for an average of 560 days (range 345-890 days), PARPi monotherapy: 254 days (range 30-750 days), and non-PARP targeted therapy: 186 days (range 24- 435 days). PD-L1 staining was completed for 38 patients; 6 patients had a PD-L1 Tumor Proportion Score > 1, although none of the patients were MSI-H or high TMB and none received immunotherapy. Conclusions: NGS testing potentially affected the treatment of 23.9% of HGSOC patients. Our division has developed a streamlined mechanism for HGSOC patients to undergo routine NGS testing with limited out-of-pocket patient cost regardless of insurance status. Given the recent upfront approval of PARPi maintenance for all HGSOC who are s/gBRCAm+, we have now integrated both germline and somatic testing during front-line therapy. More information will be required to further elucidate how LOH status affects treatment decisions and outcomes for patients. Citation Format: Nidhi Goel, Angelina I. Londono, Naveed Farrukh, Hannah M. Beer, Brandon Roane, Jaclyn Arquiette, Warner K. Huh, Charles A. Leath III, Rebecca C. Arend. Real-world usage of NGS testing in high-grade serous ovarian cancer (HGSOC)—the landscape is quickly changing [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A04.