Validation of Rapid Plasma Genotyping for Detecting EGFR and KRAS Mutations in Advanced Lung Cancer


Key Points

  • The plasma ddPCR assay had a positive predictive value of 100% for common EGFR and KRAS mutations.
  • Positive predictive value was 79% for the acquired EGFR T790M resistance mutation.

As reported in JAMA Oncology, Sacher et al have prospectively validated a plasma droplet digital polymerase chain reaction (ddPCR) assay for detecting common EGFR and KRAS mutations in patients with advanced nonsquamous non–small cell lung cancer.

Study Details

The study involved 180 patients with advanced disease, including 120 who were newly diagnosed and 60 who had acquired resistance to an EGFR kinase inhibitor. Patients underwent initial blood sampling and immediate plasma ddPCR for EGFR exon 19 del, EGFR L858R, the EGFR-acquired resistance mutation T790M, and/or KRAS G12X between July 2014 and June 2015.

All patients underwent biopsy for tissue genotyping. Tumor genotype included 80 EGFR exon 19/L858R mutants, 35 EGFR T790M, and 25 KRAS G12X mutants.

Turnaround Time and Performance

The median test turnaround time (in business days) for plasma ddPCR was 3 days (range = 1–7 days). The median turnaround time for tissue genotyping was 12 days (range = 1–54 days) for patients with newly diagnosed disease and 27 days (range = 1–146 days) for patients with acquired resistance.

Plasma ddPCR had positive predictive values of 100% for EGFR 19 del, 100% for L858R, 100% for KRAS, and 79% for EGFR T790M. Sensitivity was 82%, 74%, 64%, and 77%, respectively. Sensitivity for EGFR or KRAS was higher in patients with multiple metastatic sites and in those with hepatic or bone metastases.

The investigators concluded: “Plasma ddPCR detected EGFR and KRAS mutations rapidly with the high specificity needed to select therapy and avoid repeat biopsies. This assay may also detect EGFR T790M missed by tissue genotyping due to tumor heterogeneity in resistant disease.”

The research was supported by the U.S. Department of Defense, National Cancer Institute, Phi Beta Psi Sorority, Stading-Younger Cancer Foundation, International Association for the Study of Lung Cancer, Canadian Institutes of Health Research, Canadian Association of Medical Oncologists, Gallup Research Fund, and Kaplan Research Fund.

Adrian G. Sacher, MD, and Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute, are the corresponding authors of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.