Comprehensive Genomic Profiling Across Diverse Solid Tumors: A Real-World Experience From India With FoundationOne®CDx Testing.

Introduction Precision oncology relies on tumor-specific genomic profiling, and broad next-generation sequencing (NGS) assays such as FoundationOne®CDx (F1CDx) are increasingly used to guide targeted therapy. This study aimed to evaluate the mutational landscape, actionable alterations, and clinical utility of F1CDx testing across diverse solid tumors at an Indian oncology center. Materials and methods This retrospective study included adult patients (≥18 years) who underwent comprehensive genomic profiling with the F1CDx assay between August 2017 and April 2025. De-identified demographic, clinical, and genomic data were extracted from medical records. Somatic alterations were prioritized using a predefined hierarchy, and gene-level alteration frequencies were calculated using a binary mutation matrix. Descriptive statistics were employed to summarize all clinical and molecular findings. Genomic actionability in this study primarily reflects report-level or biological actionability, with only a subset translating into guideline-endorsed and accessible therapies in Indian practice. Results A total of 115 patients received NGS testing (67.8% female; median age was 57 years). Breast cancers (n=35), gastrointestinal malignancies (n=22), thoracic or lung (n=18), and gynecologic cancers (n=15) were most common. Distinct tissue-specific genomic signatures were observed, with recurrent convergence on MAPK, PI3K/AKT/mTOR, RTK, DNA repair, and cell cycle pathways. Breast cancers demonstrated TP53 mutations, PI3K/AKT activation, and recurrent 8p11-12/11q13 amplifications, with infrequent findings such as IDH1 R132C. Gastrointestinal cancers were dominated by KRAS/NRAS and WNT-pathway alterations, with minimal evidence of mismatch repair (MMR) deficiency. Lung cancers showed typical non-small cell lung cancer (NSCLC) driver alterations (KRAS G12D, RET fusions, PIK3CA mutations) and pervasive tumor suppressor loss, with no microsatellite instability (MSI)-high cases. Gynecologic cancers showed strong PI3K-pathway activation, TP53 disruption, and multiple amplification-driven oncogenic programs. Less frequent tumor types, including prostate, hepatobiliary, glioblastoma (GBM), head and neck, urologic cancers, and sarcomas, exhibited established genomic drivers. F1CDx recommended FDA-approved therapies relevant to the tumor type in 41.7% of cases and tumor-agnostic or off-label therapies in 50.4%. Conclusions F1CDx profiling identified a broad spectrum of actionable alterations across diverse tumors, highlighting its strong potential to expand therapeutic options and advance precision oncology in real-world Indian practice.