Progression-free survival among progressed non-small-cell lung cancer with T790M mutation as guided by liquid versus tissue re-biopsy

Abstract

Background: Osimertinib has been approved by the United States Food and Drug Administration for nonsmall-cell lung carcinoma (NSCLC) harbouring acquired T790M mutation that have progressed while on other epidermal growth factor inhibitor (EGFR)–inhibiting therapy. We compared the progression-free survival (PFS) of patients whose T790M mutation was identified by liquid biopsy with those identified by tissue sampling. Methods: This was a retrospective single-centre cohort study conducted in Queen Mary Hospital, Hong Kong. The study included 139 Chinese patients with advanced NSCLC who had disease progression after first-line EGFR tyrosine kinase inhibitor and received osimertinib upon detection of T790M mutation, either by liquid biopsy (by identification of circulating tumour DNA) or tissue re-biopsy. The primary endpoint was PFS. Results: Patients with EGFR T790M mutation detected by tissue sampling (n=37) had significantly better PFS than those detected by peripheral blood liquid biopsy (n=102) [median 380 vs 213 days, hazard ratio=0.576, 95% confidence interval=0.359-0.925, P=0.021]. A small subgroup with positive liquid biopsy but concomitant negative tissue result (n=6) had the lowest PFS among the different cohorts (median PFS=57 days). Conclusions: Tissue re-biopsy for T790M mutation is preferred for patients who have NSCLC that progressed after first-line tyrosine kinase inhibitor. For cases that only have confirmatory liquid biopsy results, clinicians should inform their patient that the expected PFS may be significantly shorter than those previously reported in literature.