Detection of EGFR mutations in circulating tumour (ct) DNA from plasma samples can be accomplished using the cobas® platform, according to findings presented at the European Lung Cancer Conference (ELCC), on 6 May, 2017 in Geneva. Assays of ctDNA offer a non-invasive 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, Lung Cancer Department, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK explained that the cobas® test is currently used in clinical practice on tumour tissue and has been approved for ctDNA EGFR testing from plasma samples, but the diagnostic performance of the test had not yet been established. 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 analysed 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 was diagnosed 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 TherascreenTM in 1% of patients. Tumour tissue was not available for 10% of patients. All plasma samples were tested on the cobas® platform.
EGFR mutations detected in ctDNA with excellent specificity
Concordance rate between tumour and ctDNA in patients with an EGFR mutation in thoracic vs extrathoracic disease.
Credit: Dr Rajiv Kumar (MBChB BMedSc FRACP)
There was good agreement between ctDNA and the tumour regarding the presence of EGFR mutation. The concordance rate between ctDNA and the tumour 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 tumour and ctDNA in patients with an EGFR mutation was 55% for thoracic-only disease and 75% for extra-thoracic disease.
Turnaround time quicker with ctDNA samples
Mutation frequency and concordance in diagnostic cohort.
Credit: Dr Rajiv Kumar (MBChB BMedSc FRACP)
Mutation frequency and concordance in acquired resistance cohort.
Credit: Dr Rajiv Kumar (MBChB BMedSc FRACP)
The mean time to EGFR result was shorter for ctDNA samples, at 8.4 days, than for tumour 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 2 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.
Discussant point: S. Lantuejoul who discussed the study results at the poster discussion session, presented a new algorithm for EGFR mutated patients for T790M mutation detection. In the case of EGFR tyrosine kinase inhibitor acquired resistance, liquid biopsy for T790M mutation detection is indicated. In the case of T790M positive disease, osimertinib without biopsy is indicated. In the case of T790M negative disease, a biopsy should be done and if T790M is found then osimertinib is a treatment choice, but in the case of T790M negative disease, chemotherapy should be further treatment.
Disclosure
Funding from Roche Molecular Solutions CA, USA was reported.