ELCC 2017: Prospective Study Shows Concordance of EGFR Mutation Detection Between ctDNA and Tumor Samples

Key Points

  • The concordance rate between ctDNA and the tumor was 87%, with sensitivity of 65% and specificity of 98%.
  • The positive predictive value was 95%, and the negative predictive value was 85%.
  • The mean time to EGFR result was shorter for ctDNA samples, at 8.4 days, than for tumor tissue, which took 11.2 days.

Detection of EGFR mutations in circulating tumor (ct) DNA from plasma samples can be accomplished using the cobas platform, according to findings presented by Kumar et al at the 2017 European Lung Cancer Conference (ELCC) (Abstract 95PD). Assays of ctDNA offer a noninvasive method of finding EGFR mutations that can guide the clinical decision to offer EGFR inhibitor treatment to a patient with non­–small cell lung cancer (NSCLC).

Rajiv Kumar, MD, of the Lung Cancer Department, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, explained that the cobas test is currently used in clinical practice on tumor tissue and has been approved for ctDNA EGFR testing from plasma samples, but the diagnostic performance of the test had not yet been established.

Study Details

He headed a team that conducted this prospective study using data from patients diagnosed with advanced NSCLC at the Royal Marsden Hospital between November 2015 and November 2016 to evaluate the diagnostic performance of the cobas platform on ctDNA in plasma samples. To be included in the dataset, patients were required to have an available tissue EGFR result. Peripheral blood samples were collected in cell-free DNA detection (cfD) tubes and analyzed using the cobas platform per manufacturer’s instructions.

The median age of patients in the study was 68 years. Adenocarcinoma was diagnosed in 89% of patients, poorly differentiated carcinoma in 4%, squamous cell carcinoma in 3%, adenosquamous in 2.5%, and other lung cancer histology in 1.5% of patients. The smoking status was never-smoker in 30% of patients, while 58% were ex-smokers, 10% were current smokers, and 2% of patients had an unknown smoking history. Stage IV disease was reported in 93% of patients, and stage III disease was seen in 7% of patients. Thoracic-only disease was observed in 42% of patients.

The tissue EGFR analysis had been performed on the cobas® platform in the majority (79%) of patients, while EGFR analysis had been done using Illumina NGS in 7.5% and Therascreen in 1% of patients. Tumor tissue was not available for 10% of patients. All plasma samples were tested on the cobas platform.

Findings

There was good agreement between ctDNA and the tumor regarding the presence of EGFR mutation. The concordance rate between ctDNA and the tumor was 87%, with sensitivity of 65% and specificity of 98%. The positive predictive value was 95%, and the negative predictive value was 85%.

The concordance rate between tumor and ctDNA in patients with an EGFR mutation was 55% for thoracic-only disease and 75% for extra-thoracic disease.

The mean time to EGFR result was shorter for ctDNA samples, at 8.4 days, than for tumor tissue, which took 11.2 days (p = 0.07). The failure rate for ctDNA samples was just 2.4%.

EGFR mutations in exon 19 and T790M were detected only in plasma ctDNA due to tissue failures involving two samples.

Conclusions

This study confirmed that ctDNA may be used for diagnosis of an EGFR mutation in advanced NSCLC with excellent specificity and moderate sensitivity. The authors recommended that the cobas test for ctDNA be incorporated into clinical practice to triage patient care.

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®.


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