Abstract 720: Clinical actionability of an Asian pan-cancer tissue-based next generation sequencing (NGS) assay
Authors: Jing Yi Lee, Aya E. Helali, Zi Yi Wan, Donald Y. Poon, Jens Samol, Tsz Him So, Su Pin Choo, Ravindran Kanesvaran, Cheng-Vai Hui, Joseph S. Au, Timothy Yip, Ross Soo, Michelle Pek, Ruifen Weng, Bin Tean Teh, Min-Han Tan, Jonathan Poh, Jason Y. Chan
Journal: Cancer Research (2025)

Abstract Introduction: While traditionally informed by tumor tissue origin and histopathology, advancements in next-generation sequencing (NGS) technology have catalyzed tumor-agnostic approaches which prioritize molecular alterations for personalized treatment. Here, we demonstrate the clinical utility of molecularly guided tumor-agnostic precision medicine in an Asian cohort, leveraging an Asian-centric NGS panel tailored to address the unique genetic landscape of the region. Methods: 1,167 formalin-fixed paraffin-embedded tissue samples from 1,150 Asian cancer patients across &amp;gt;70 centers in 7 countries underwent real-world NGS testing using an Asian-centric pan-cancer hybrid-capture NGS panel (UNITED), profiling 572 cancer-related genes and 91 RNA fusion partners. Biomarkers were classified as actionable if therapeutic indications were FDA-approved, guideline-recommended, or supported by robust phase III clinical trials. Results: The cohort encompassed 23 cancer types, with lung (17.7%), colorectal (12.8%), prostate (11.1%), and breast (8.6%) cancers accounting for 50.1% of the clinical volume. Actionable biomarkers were identified in 62.2% of samples, with KRAS, EGFR, and PIK3CA among the most frequently mutated genes. The likelihood of identifying ≥1 actionable mutation was highest in CNS tumors (83.6%), followed by lung cancer (81.2%), breast cancer (79%), and others. Among 27,552 somatic variants detected, 1,291 (4.7%) were potentially targetable by regulatory-approved therapies. Notably, ≥1 tumor-agnostic biomarker (including TMB-H, dMMR/MSI-H, NTRK/RET fusions, and BRAF V600E) was identified in every cancer type, detected in 98 samples (8.4%). This includes in 16.9% of lung tumors, 12.2% of tumors of unknown primary origin, 11.8% of endometrial tumors, and others. As expected, TMB was significantly associated with MSI (p&amp;lt;0.0001). ERBB2 amplification, a potential surrogate marker for HER2 overexpression, was identified in 42 samples (3.6%) and was most frequently detected in breast tumors (15%), followed by endometrial tumors (11.8%), ovarian tumors (8.9%), and others. Homologous recombination deficiency (HRD) was observed in 407 samples (34.9%) and were present in about half of the tumors of the breast (50%), colon (49%), urothelium (47.1%), endometrium (47.1%) and lung (44%). Notably, HRD-positive tumors exhibited significantly higher TMB compared to HRD-negative tumors (median TMB 5.58 vs. 5.15, p=0.0001). Conclusion: Leveraging an Asian-centric NGS panel, actionable molecular alterations were detected in 62.2% of Asian cancer patients. The high prevalence of actionable biomarkers, coupled with the detection of regulatory-approved tumor-agnostic markers, underscores the significance of comprehensive NGS testing in facilitating tumor-agnostic precision medicine in an Asian setting, thereby improving treatment strategies and patient outcomes. Citation Format: Jing Yi Lee, Aya E. Helali, Zi Yi Wan, Donald Y. Poon, Jens Samol, Tsz Him So, Su Pin Choo, Ravindran Kanesvaran, Cheng-Vai Hui, Joseph S. Au, Timothy Yip, Ross Soo, Michelle Pek, Ruifen Weng, Bin Tean Teh, Min-Han Tan, Jonathan Poh, Jason Y. Chan. Clinical actionability of an Asian pan-cancer tissue-based next generation sequencing (NGS) assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 720.