Adding plasma NGS testing to routine NSCLC management could aid targeted therapy delivery
medwireNews: Plasma-based next-generation sequencing (NGS) may help to identify therapeutically targetable mutations in patients with metastatic non-small-cell lung cancer (NSCLC), suggests research published in JAMA Oncology.
Plasma-based circulating tumor DNA NGS alone was performed in 94 (29.1%) of 323 patients with stage IV NSCLC, with therapeutically targetable mutations found in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2, or BRAF for 31 (33.0%) – alleviating the need for an invasive tissue biopsy.
In the remaining 229 patients who underwent concurrent plasma and tissue NGS or were unable to have tissue NGS , targetable mutations were found in tissue alone in 47 (20.5%) patients, while the addition of plasma testing increased this number to 82 (35.8%). And of 42 patients who were treated with targeted therapy based on their plasma NGS result, 36 (85.7%) achieved disease control, with a complete response in one patient, a partial response in 19 patients and stable disease in 16.
This “clearly demonstrates that liquid biopsy can improve delivery of therapy and, consequently, outcomes,” say Erica Carpenter (University of Pennsylvania Perelman School of Medicine, USA) and co-researchers.
In an accompanying editorial, Bishal Gyawali (Harvard Medical School, Boston, Massachusetts, USA) and Howard (Jack) West (Swedish Cancer Institute, Seattle, Washington, USA) similarly noted: “The study compellingly demonstrates that plasma NGS can obviate the need for tissue NGS in patients in whom plasma testing demonstrates a mutation, given the response and disease control rate among patients who had therapeutically targetable mutations identified from plasma.”
They continued: “These results, combined with the patient satisfaction with the relative ease of providing blood rather than a solid tissue sample, suggest a clinical strategy of pursuing plasma NGS first, then tissue NGS if plasma NGS cannot detect relevant mutations.”
Overall concordance between plasma and tissue testing was 81.3%, with significantly higher concordance among the 166 patients tested at diagnosis compared with the 157 tested at disease progression (88.9 vs 70.2%).
A novel observation, say the researchers, was a high concordance rate of 100% between plasma and tissue testing in patients patients with liver metastases, whereas in patients with disease limited to the thoracic cavity the concordance rate was lower, at 46.2%
“These results suggest that adding plasma NGS to tissue NGS can enhance the detection of therapeutically targetable mutations but may vary by location of metastatic disease,” the team comments.
The researchers conclude: “To keep up with rapid therapeutic progress in the molecular diagnosis and treatment of NSCLC, we must incorporate safe and facile noninvasive methods for sensitive, comprehensive tumor profiling to select patients for personalized therapy.
“Given the ease of obtaining plasma-based genotyping and the success observed with such a noninvasive approach, our results argue for incorporation of plasma-based genotyping into routine clinical management of patients with NSCLC.”
By Catherine Booth
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