1215P EGFR-mutated squamous cell lung cancer and its association with outcomes

Abstract

Background: Liquid biopsies have been shown to be reliable as a complementary tool to demonstrate tumor relation mutations. High procedure cost and sub-optimal sensitivity have been hurdles to public funding of this technique in Canadian centers. The CLEAR trial was designed to evaluate the clinical and economic impact of early diagnosis with circulating fragments of DNA (cfDNA) EGFR testing for suspected lung cancer patients. The objectives are to demonstrate clinically relevant improved time to detection of an EGFR mutation, evaluate the impact of cfDNA diagnosis on patient investigation and time to initiate specific EGFR inhibitor therapy.Methods: After obtaining their consent, patients were included while undergoing investigation for a radiological suspicion of stage III/IV advanced lung cancer. CfDNA were extracted from plasma and analyzed for EGFR mutation using CobasÒ EGFR Mutation Test v2. Results:The results of the first 100 patients, out of 600 planned, recruited between November 2019 and January 2021 are reported. Median age was 65 years (range: 34-95) and 52% were female. Adenocarcinoma was confirmed in 67% of cases and 75% of the cohort had stage IV disease. About 9% of patients had no adequate tissue to perform molecular analysis and 10% of patients had undergone at least 2 biopsies. The median time to results was significantly shorter by cfDNA (median time to results: 7 vs 27 days, p<0.0001). Rate of mutations detected was 9% and 11% by cfDNA and tissue biopsy respectively. Mutation detection by cfDNA is 84.6% sensitive and 100% specific. Osimertinib was initiated within 2-27 days of the cfDNA results and 0-21 days before the tissue diagnosis in 5/9 patients. Pan cranial radiotherapy was avoided in 3 out of 4 patients with brain metastases using cfDNA results and allowed one patient with Ex20 insertion to be referred rapidly to a clinical trial.Conclusions: EGFR mutation detection by cfDNA and tissue biopsy are complementary. Early detection by cfDNA can improve time to diagnosis and accelerate appropriate therapy. Our preliminary evaluation suggests that even earlier use of cfDNA may further improve time to treatment.