Genomic Profiling of Advanced Solid Tumors Supported by New Study

Genomic Profiling of Advanced Solid Tumors Supported by New Study
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Can genomic profiling help improve outcomes of advanced cancer patients? A new study says that it most cases it can.

The Michigan Oncology Sequencing Program (Mi-ONCOSEQ), previously reported on 500 patient study that showed Pathogenic germline variants (PGVs) were identified at a high rate (12.2%) and that DNA and RNA sequencing both helped identify clinically actionable targets.

Now, with an expanded cohort of more than 1000 patients linked to clinical outcomes, the team has shown which patients derived the greatest clinical benefit from sequencing-directed therapy (SDT).

In this cohort study of 1015 patients who underwent integrative genomic profiling, most of the patients derived substantial clinical benefit from sequencing information.

These findings, the researchers say, support directed germline testing for inherited cancer predisposition in all patients with advanced cancer and also support the use of integrative genomic profiling as a component of standard of care for patients with cancer of unknown origin and other rare malignant neoplasms.

Targeted therapy has improved clinical outcomes across a wide range of malignant neoplasms. Examples include EGFR-mutant non–small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors, ERBB2 (formerly HER2/neu)-amplified breast cancer treated with human epidermal growth factor receptor 2–specific antibodies, and tumors with microsatellite instability treated with immune checkpoint blockade.

As a result, interest in next-generation sequencing (NGS) testing for advanced solid tumors to identify patients who qualify for biomarker-selected clinical trials is increasing. NGS is being offered commercially and on institutional platforms.

But the efficacy studies of these tests have, so far, produced varied results, and in part that is a result of the tests themselves. Some are limited to DNA-based testing of a select group of known, targetable cancer-related genes. Others use unbiased, comprehensive DNA- and RNA-based analyses of samples consisting of tumor and normal samples, with additional goals of identifying novel somatic alterations or pathogenic germline variants (PGVs) conferring increased cancer risk.

Studies of comprehensive NGS testing in patients with advanced cancer report a wide range of clinically actionable genomic alterations per patient, ranging from 40% to 94%. Furthermore, many studies note that only 10% to 25% of patients receive therapy informed by sequencing, making it challenging to assess the degree of clinical benefit gained.

But, the researchers say, the high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.