Abstract C054: Clinical Utility of Comprehensive Genomic and Transcriptomic Analysis to Guide Therapy for Patients with Metastatic Solid Tumors

Abstract Background: Precision oncology, defined as molecular profiling of an individual’s tumor to guide therapy, has rapidly evolved in the past few decades with the advancement of NGS technologies. Since not all patients’ tumors show targetable DNA alterations, a comprehensive genomic and transcriptomic profiling (CGTP) approach is warranted to provide therapy options for patients beyond those with actionable DNA alterations. Here, we conducted a prospective study to determine the added value of CGTP using BostonGene Tumor Portrait™ test in identifying actionable DNA and RNA alterations and therapy selection for patients who have had targeted panel sequencing (TPS) on an institutional panel. Methods: 117 patients with advanced solid tumors who had prior TPS, and no College of American Pathologists (CAP) Tier-1 actionable targets underwent CGTP between August 2022 and October 2024 at MD Anderson Cancer Center. A CGTP biomarker result was considered actionable if it was therapeutically targetable or predictive of response or resistance to a clinically available therapy. Patients matched to CGTP-informed therapies were evaluated for clinical benefit. Results: 99 patients (84.6%) were included in the final analysis, while 18 patients (15.4%) were screen failed due to tissue insufficiency or incomplete data. Median turn-around time from consent to sample acquisition (SA) and from SA to CGTP report were 14 and 15 days, respectively. Median age of the patients was 50 years (13-74). Fifty-four (54.5%) patients were female and 78 (78.8%) were white. Head and neck (26.3%), sarcoma (19.2%), ovarian (8.1%) and mesothelioma (7.1%) were the most common histologies. Median prior lines of therapy in the metastatic setting was 3 (0-13). CGTP identified at least one actionable DNA alteration not captured by prior TPS for 59 (59.6%) cases. Of those variants, 43.8% were deletions, 26% amplifications and 15.6% SNVs. CGTP found previously undocumented pathogenic germline variants for 3 (3.0%) cases. Actionable RNA expressions (AREs) were identified for all 99 patients with a median ARE of 22 (interquartile range (IQR), 17.0-26.0). The majority of AREs were RNA overexpressions (86.0%). Of 33 patients with actionable copy number alterations (CNAs), 16 (48.5%) had concomitant AREs in the corresponding genes. Of 11 patients with AREs who also had IHC, 7 (63.6%) had corresponding actionable protein expressions. Forty patients had a treatment change after CGTP, 19 of whom (47.5%) received CGTP-matched therapies (12 DNA matches and 7 RNA matches) at the time of data cut-off, for whom the overall response rate and clinical benefit rate were 15.8% and 31.6%, respectively. The median progression-free survival was 4.0 months (IQR, 2.0-8.0). Conclusions: Our data shows the feasibility and utility of CGTP to match patients to molecularly informed treatments within a clinically relevant time frame. Transcriptome analysis not only confirms actionable CNAs but also helps identify changes in the expression of novel therapeutic targets, enhancing opportunities for precision oncology. Citation Format: Burak Uzunparmak, Fei Su, Amber M. Johnson, Kenna R. Shaw, Elisabeth Kathleen. Kong, Anil Korkut, Camila Braganca-Xavier, Ying Yuan, Nathan Fowler, Francesca Paradiso, Lile Kontselidze, Anna Butusova, Aleksander Bagaev, Ecaterina E. Dumbrava, Jordi Rodon-Ahnert, David S. Hong, Siqing Fu, Timothy Anthony. Yap, Aung Naing, Sarina Anne. Piha-Paul, Renata Ferrarotto, Bryan Iorgulescu, Shashikant Kulkarni, Keyur P. Patel, Funda Meric-Bernstam. Clinical Utility of Comprehensive Genomic and Transcriptomic Analysis to Guide Therapy for Patients with Metastatic Solid Tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C054.