Liquid biopsy shows promise

The study by Sacher et al published in JAMA Oncology reported on “a blood test” that detects EGFR and KRAS mutations with rapid plasma genotyping of cell free DNA.

The objective of their study was to prospectively validate plasma droplet digital PCR (ddPCR) for the rapid detection of common epidermal growth factor receptor (EGFR) and KRAS mutations, as well as the EGFR T790M acquired resistance mutation.

Patients with advanced non-squamous non–small-cell lung cancer (NSCLC) who either had a new diagnosis and were planning period for initial therapy or had developed acquired resistance to an EGFR kinase inhibitor and were planned for rebiopsy underwent initial blood sampling and immediate plasma ddPCR for EGFR exon 19 del, L858R, T790M, and/or KRAS G12X between July 3, 2014, and June 30, 2015, at a National Cancer Institute–designated comprehensive cancer center. All patients underwent biopsy for tissue genotyping, which was used as the reference standard for comparison; rebiopsy was required for patients with acquired resistance to EGFR kinase inhibitors. Test turnaround time (TAT) was measured in business days from blood sampling until test reporting.

Of 180 patients with advanced NSCLC (62% female; median [range] age, 62 [37-93] years), 120 cases were newly diagnosed; 60 had acquired resistance. Tumor genotype included 80 EGFR exon 19/L858R mutants, 35 EGFR T790M, and 25 KRAS G12X mutants. Median (range) TAT for plasma ddPCR was 3 (1-7) days. Tissue genotyping median (range) TAT was 12 (1-54) days for patients with newly diagnosed NSCLC and 27 (1-146) days for patients with acquired resistance. Plasma ddPCR exhibited a positive predictive value of 100% for EGFR 19 del, 100% for L858R, and 100% for KRAS, but lower for T790M at 79%.  The sensitivity of plasma ddPCR was 82 for EGFR 19 del, 74% for L858R, and 77% for T790M, but lower for KRAS at 64%. Sensitivity for EGFR or KRAS was higher in patients with multiple metastatic sites and those with hepatic or bone metastases, specifically.

In conclusion, plasma ddPCR detected EGFR and KRAS mutations rapidly with the high specificity needed to select therapy and avoid unnecessary biopsies. The test accurately provided the information whether a patient with NSCLC lung cancer had a mutation that makes the disease treatable. It could also tell if less-fortunate patients had a different mutation, saving them weeks or months of treatment that would ultimately failed.  Finally, the noninvasive genotyping provides physicians with all the information they need thus the inherent risks of tissue genotyping due to repeated biopsies are avoided.