1425P - Clinical utility of liquid biopsy for the early diagnosis of EGFR mutant advanced lung cancer in real-life setting (CLEAR)

Background

Timely diagnosis with complete molecular profiling is essential in advanced lung cancer. Although tissue sampling remains the gold standard, liquid biopsies provide an alternative option for timely molecular characterization, especially for epidermal growth factor receptor (EGFR) testing in lung cancer.

Methods

All patients referred at the Centre Hospitalier de l’Université de Montréal (CHUM) with a radiological suspicion of advanced lung cancer and no known prior tumour molecular testing were prospectively screened and consented. Plasma and tissue samples were retrieved for EGFR testing and mutations were analyzed using Cobas® cell-free DNA (cfDNA). The CLEAR study evaluated plasma and tissue EGFR testing and the clinical impact on the management of suspected lung cancer patients.

Results

Between November 2019 and January 2023, a total of 312 patients were initially screened for eligibility for inclusion in the study and 7 patients were excluded for history of treated lung cancer. Median age was 68 years, 55% were female, 17% were non-smokers, and 30% were active smokers. 83% had non-small cell lung cancer and 70% of patients had stage IV disease. 8% and 10% EGFR mutations were detected by cfDNA and tissue biopsy, respectively. EGFR exon 19 deletion was the most frequent mutation, detected in 59% of patients. Median time to EGFR result was 28 days and 3 days for tissue and plasma sampling, respectively. cfDNA was 100% specific and 72% sensitive for EGFR status. Positive predictive value was 100% and the negative predictive value was 95%. Osimertinib was initiated within a median of 12 days of cfDNA results and up to 21 days before tissue results. Cranial radiotherapy was avoided in 6 EGFR-positive patients with brain metastases.

Conclusions

Early detection of EGFR mutations by cfDNA reduces time to diagnosis and accelerates therapy initiation. Cobas® assay is specific, with high positive and negative predictive values. Decreased delays to access targeted therapy can decrease improper treatment choices and alleviate complications of untreated disease while awaiting molecular results from tissue biopsies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

Y. Kim, I. Syed, N. Devost, G. Kenth: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Hui: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Blais: Financial Interests, Personal, Funding: AstraZeneca. All other authors have declared no conflicts of interest.