Liquid biopsy—a noninvasive blood test—was able to genotype 2 key mutations in the epidermal growth factor receptor (EGFR) and KRAS genes associated with newly-diagnosed, advanced nonsquamous non-small cell lung cancer (NSCLC) with 100% certainty, according to a prospective study published in JAMA Oncology.1

Compared with tissue biopsies, which required a median of 12 days for genotyping newly diagnosed NSCLC and 27 days for acquired resistance, the blood test was able to detect the same mutations in 3 days.

“Liquid biopsy to detect circulating tumor DNA was developed in the hope of getting a test that was rapid, thereby accelerating delivery of care,” corresponding author Geoffrey Oxnard, MD, thoracic oncologist and lung cancer researcher at the Dana-Farber Cancer Institute and the Brigham and Women’s Hospital in Boston, told Cancer Therapy Advisor.

An accompanying editorial admits that liquid biopsies offer a powerful tool for cancer treatment, but contend that more studies like this need to be done before it can replace tissue biopsies.2

Having earlier piloted and validated it for clinical use specifically for NSCLC, researchers used the droplet digital polymerase chain reaction (ddPCR) on blood samples to genotype for EFGR exon 19 del, L858R, and KRAS G12X mutations in newly-diagnosed NSCLC and EFGR exon 19 del, L858R, and T790M in resistant NSCLC.

Of 180 patients with advanced NSCLC—120 were newly diagnosed and were planned for initial treatment; 60 had acquired mutations to an EGFR kinase inhibitor. The genotypes obtained from ddPCR were compared with those obtained from tissue biopsy, which was the reference and provided treatment guidance to oncologists who were blinded to the results of the ddPCR.

In patients where mutations were detected with ddPCR, blood samples were taken at 1 to 2 weeks and 4 to 6 weeks after beginning therapy.

Plasma ddPCR detected genotypes for newly-diagnosed NSCLC with 100% specificity—101 of 101 for EGFR exon 19 del and 102 of 102 for L858R, and 62 of 62 for KRAS G12X. Positive predictive value (PPV) was 100%.

However, with a PPV of 79% for the EGFR T790M mutation, the blood test was able to pick up mutations that were not seen in a tissue biopsy.

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“Due to tumor heterogeneity, tissue genotyping may not be the best reference standard for tumors that have acquired resistance,” lead author Adrian G. Sacher, MD, now at Columbia University, told Cancer Therapy Advisor.

Dr Oxnard explained that resistant tumors may carry different mutations in different parts of the tissue and it is possible that a single biopsy will not pick up all the mutations.