Mutational landscape of ovarian cancers (OC) identified by prospective clinical sequencing in a nationwide cancer network.

Abstract

e17067 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of OC assayed in a nationwide cancer network. Methods: 449 Pts with advanced OC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant (CR) GA were defined as associated with targeted therapies or mechanism-driven clinical trials. Treatment histories for the 449 patients were obtained with IRB-approved retrospective review. Results: Median age was 56 years (range, 23-83), 71% were Caucasian. GA were identified in 94% (420/449) of OC, of which 283 (63%) had a clinically relevant genomic alteration (CRGA). 24.0% in HRD ( BRCA1/2, ATM, PALB2, BRIP1). CRGA in other potentially targetable pathways were identified: 48.0% MEK pathway ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) CRGA, 33.5% PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7), and 10.6% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). All OC tested were microsatellite stable and only one patient had a tumor mutational burden > 20 muts/Mb. 21% (59/283) of OC patients were ordered a genomically-matched treatment, 58% (37/64) were agents that were FDA approved in a different tumor type, and 17% (11/64) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. For the off label non-study population the median PFS was 19 weeks, and the median OS was 34 weeks. Conclusions: In a large series of OC assayed with CGP, 21% of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.