Abstract 939: Comprehensive genomic and transcriptomic analysis to guide therapy for patients with metastatic solid tumors
Authors: Burak Uzunparmak, Fei Su, Amber M. Johnson, Krystle Nomie, Nathan Fowler, Lile Kontselidze, Aleksander Bagaev, Anna Butusova, Ecaterina E. Dumbrava, Jordi Rodon-Ahnert, Siqing Fu, David S. Hong, Timothy A. Yap, Aung Naing, Sarina A. Piha-Paul, Daniel D. Karp, Paula R. Pohlmann, Apostolia M. Tsimberidou, Keyur P. Patel, Funda Meric-Bernstam
Journal: Cancer Research (2024)

Abstract Introduction: Precision oncology, which aims to profile tumors for identifying actionable alterations to guide therapy has become mainstream in cancer clinics. While most approaches focus on DNA aberrancies on targeted panels, not all patients’ tumors show targetable genomic alterations in these limited gene sets, indicating a need for more comprehensive methodologies combining whole exome (WES) and transcriptome sequencing (RNAseq) to direct a larger fraction of patients to therapies. Here, we aimed to compare the feasibility and utility of BostonGene’s (BG) analytical platform with WES and RNAseq to two targeted exome panels in identifying actionable alterations and therapy selection for patients with metastatic solid tumors. Methods: Study enrolled patients with solid tumors who have had next-generation-sequencing (NGS) testing with one of two tissue-based targeted exome sequencing panels, Oncomine (ThermoFisher, 148 genes), or MDA-MAPP (615 genes) with identification of no College of American Pathologists Tier-1 actionable DNA alterations between August 2022 and November 2023. Patients’ tissue and blood/saliva samples were subjected to BG’s NGS platform. An alteration-level actionability analysis was done upon receipt of WES results to inform treatment decision making, based on functional and therapeutic effects of the alterations detected. Results: A total of 64 patients were enrolled; testing was cancelled for 7 patients (10.9%) with samples showing &amp;lt;10% tumor content, while 5 patients’ reports were pending at the time of data analysis. Median turn-around time from consent to sample acquisition (SA) and from SA to available genomic profile were 8 and 15.5 days, respectively. 52 patients had NGS results representing a diverse group of tumor types, including sarcoma (n=11, 21.2%), head and neck (n=9, 17.3%) and mesothelioma (n=5, 9.6%). BG reported DNA alterations (mean: 3.75; median: 4) not shown by prior testing for 94.2% (49/52) of patients, whereby the most common alteration types included SNVs (43.1%), deletions (23.6%) and amplifications (11.8%). BG identified additional actionable DNA alterations (referred to as “AAs”; mean: 1.9, median: 2) in 32 (61.5%) patients, whereby majority of AAs were deletions (59.7%) and amplifications (27.4%). BG detected AAs in 58.8% (10/17) vs 62.9% (22/35) of patients for whom the same vs different samples were used across different tests compared (P=0.8). Of 32 patients with AAs, 7 (21.9%) were directed to DNA-informed treatments within 6 months based upon the new genomic findings reported by BG, 14 (43.8%) are being followed for treatment matching, while 11 (34.4%) were deceased. Discussion: Our results show the feasibility and utility of comprehensive molecular testing to match patients to WES-informed treatments within a clinically relevant time frame. Assessment of the additional benefit of RNA expression analysis is forthcoming. Citation Format: Burak Uzunparmak, Fei Su, Amber M. Johnson, Krystle Nomie, Nathan Fowler, Lile Kontselidze, Aleksander Bagaev, Anna Butusova, Ecaterina E. Dumbrava, Jordi Rodon-Ahnert, Siqing Fu, David S. Hong, Timothy A. Yap, Aung Naing, Sarina A. Piha-Paul, Daniel D. Karp, Paula R. Pohlmann, Apostolia M. Tsimberidou, Keyur P. Patel, Funda Meric-Bernstam. Comprehensive genomic and transcriptomic analysis to guide therapy for patients with metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 939.