Next-generation sequencing was found to benefit a subset of patients with advanced solid tumors, according to the results of a prospective cohort study published in JAMA Oncology.

Known as the Michigan Oncology Sequencing Program (Mi-ONCOSEQ), the cohort study included 1015 patients with advanced solid tumors who underwent tumor biopsy and blood sampling. Next-generation sequencing was performed to identify variants and potentially guide treatment. Medical records were reviewed to determine response to sequencing-directed therapy.

The average age of participants in the study cohort was 57.7 years, with similar representation of men and women (53.0% vs 47.0%).

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Overall, 817 patients (80.5%) had potentially clinically actionable genomic alterations, which led to sequencing-directed therapy for 132 patients (16.2%).

Among 132 patients who had sequencing-directed therapy, 49 derived clinical benefit, which meant receipt of therapy for at least 6 months. Clinical benefit was most commonly seen in patients with sarcoma, prostate adenocarcinoma, and carcinoma of unknown primary. Most patients were treated with targeted small-molecule inhibitors (70.5%) or immune checkpoint inhibitors (22.0%).

A subset of 26 patients who received sequencing-directed therapy had exceptional responses, which meant receipt of therapy for at least 12 months.

Pathogenic germline variants were identified in 160 patients (15.8%), of whom 49 (4.8%) had variants with therapeutic targets. Most patients did not know they had pathogenic germline variants before the study.

The study authors concluded that the “high rate” of “therapeutically relevant” pathogenic germline variants identified across cancer types “supports a recommendation for directed germline testing in all patients with advanced cancer.”


Cobain EF, Wu Y-M, Vats P, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. Published online February 21, 2021. doi:10.1001/jamaoncol.2020.7987