Reflexed molecular testing to identify patients with biomarkers associated with tumor-agnostic FDA drug approvals.

Abstract

e15160 Background: Advances in genomic technology and the development of an increased repertoire of targeted treatments are helping achieve better outcomes for patients with cancer. Sequencing may expose a genomic target that would not have been predicted based on patients’ cancer histology results alone. The results of basket clinical trials focusing on all solid (Pan-Solid) tumors have led the FDA to approve some drugs based on a particular genomic target regardless of histology. Methods: We analyzed the comprehensive molecular genomic profiling of FFPE tumor samples sent to a commercial CLIA-certified laboratory from our private cancer institute since 2016. Profiling included whole exome and transcriptome sequencing, as well as immunohistochemistry (IHC). cBioPortal is a Cancer Genomics database that provides visualization, interrogation, and analysis of cancer genomics datasets. We retrospectively queried our instance of cBioPortal for Pan-Solid FDA-approved biomarkers. Results: As of January 9, 2025, we have data from 6,773 solid tumor samples in 5,855 patients. In total, 632/5,855 (10.8%) patients harbored at least one indication for which there is a tumor agnostic FDA drug approval, including 288 patients whose tumors had high tumor mutational burden (TMB-H), for which immunotherapy is FDA-approved, 115 had tumors with a BRAF V600E mutation for which BRAF-targeted therapy is approved, 18 with RET fusion (RET targeted therapy), and 6 with fusions in NTRK1/2/3 genes. We identified 144 patients whose tumors exhibited microsatellite instability (MSI-H), and 92 with deficient mismatch repair (dMMR). Lastly, 33 had HER2 IHC-positive tumors. We assessed the treatment history of the patients with tumor alterations that are not commonly associated with the identified biomarker. One patient with colorectal cancer ( RET fusion/dMMR/MSI-H, and TMB-H) is receiving immunotherapy. While most patients were provided standard-of-care treatment (SOC), 7 of 19 patients with a BRAF V600E mutation who were diagnosed with cancers other than lung, melanoma, and thyroid cancers started targeted therapy based on this finding. Three patients discontinued treatment due to toxicity; one patient was recently started on dual BRAF inhibition and the rest resumed SOC treatment. Conclusions: Although most patients were provided SOC treatment, the option of targeted therapy is available. Additional studies are needed to determine whether initial targeted therapy would be more beneficial than SOC cytotoxic treatment. The use of somatic testing is increasing with an increased understanding of the potential clinical utility of molecular testing.