# Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer

Source: https://onco.cc/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/  
OnCo record `paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding a blood test to routine practice nearly doubled the number of patients found to have a treatable mutation, and a third of those tested by blood alone were spared a biopsy.

## Summary

A prospective cohort of 323 patients with metastatic non-small-cell lung cancer had plasma next-generation sequencing on a 73-gene platform ordered as part of routine clinical management. Therapeutically targetable mutations in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2 or BRAF were detected in 113 patients overall, 35.0%. Ninety-four patients had plasma testing only, and a targetable mutation was found in 31 of them, 33.0%, sparing an invasive biopsy. Among the remaining 229 patients who had concurrent plasma and tissue testing or could not have tissue testing, a targetable mutation was detected in tissue alone for 47 patients, 20.5%, and the addition of plasma raised this to 82, 35.8%. Thirty-six of 42 patients treated on the basis of a plasma result achieved a complete or partial response or stable disease.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: JAMA Oncology
- Year: 2019
- DOI: 10.1001/jamaoncol.2018.4305
- Authors: Aggarwal C, Thompson JC, Black TA, et al.
- Findings: Targetable mutations in 35.0% of patients overall with plasma sequencing in routine use.; Plasma-only testing found a targetable mutation in 33% of those patients, avoiding a biopsy.; Adding plasma to tissue raised detection from 20.5% to 35.8%.; Thirty-six of 42 patients treated on a plasma result responded or remained stable.
- What it means: It showed the benefit of plasma testing is not only analytical but logistical: it reaches patients who are too unwell, or whose disease is too inaccessible, for a repeat biopsy.
- Caveats: Single centre, not randomised, and testing was at physician discretion.; Allele fraction did not correlate with depth of response.; Median follow-up was seven months.

## Sources

- Aggarwal et al., JAMA Oncol 2019: plasma-based genotyping and the delivery of matched treatment in 323 metastatic lung cancers: https://doi.org/10.1001/jamaoncol.2018.4305
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30325992/

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [ALK](https://onco.cc/targets/alk/), [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/), [HER2](https://onco.cc/targets/her2/), [MET](https://onco.cc/targets/met/), [RET](https://onco.cc/targets/ret/), [ROS1](https://onco.cc/targets/ros1/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Biopsy](https://onco.cc/terms/biopsy/), [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)

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