Combined plasma and tissue genotyping of EGFR T790M benefits NSCLC patients: a real‐world clinical example

Abstract

Acquired resistance to epidermal growth factor receptor ( EGFR )‐tyrosine kinase inhibitors ( TKI s) is a prevalent clinical problem in the management of advanced non‐small‐cell lung cancer ( NSCLC ) with TKI ‐sensitizing mutations in the EGFR gene. Third‐generation EGFR ‐ TKI s have demonstrated potent activity against TKI resistance mediated by the EGFR T790M mutation, and standard rebiopsy and liquid biopsy are utilized to assess the T790M status of the NSCLC patients who experienced progressive disease (PD). Here, we conducted a retrospective study to assess 375 patients whose initial biopsy indicated a TKI ‐sensitizing mutation (either EGFR 19del or L858R) and who developed PD after treatment with first‐generation TKI s, and assayed for T790M status. We adopted a combination approach in which tissue rebiopsy is preferred, utilizing liquid biopsies when tissue rebiopsy is not feasible. We analyzed the potential predictive clinical factors affecting T790M detection, evaluated the standard rebiopsy and liquid biopsy methods in T790M genotyping, and reported the clinical performance of osimertinib. Our results suggested that primary EGFR 19del, brain metastasis, and longer progression‐free survival of initial EGFR ‐ TKI treatment are associated with acquired T790M resistance. T790M‐positive patients significantly benefited from osimertinib. In conclusion, the real‐world clinical adoption of the combination approach with both tissue rebiopsy and liquid biopsy for T790M genotyping may provide significant benefits to patients who have developed PD after first‐generation TKI treatments.

Liquid Biopsy for EGFR Mutation Analysis in Advanced Non-Small-Cell Lung Cancer Patients: Thoughts Drawn from a Real-Life Experience

“…Perhaps, the use of ddPCR is more appropriate for confirmation of the results from tumor biopsy, given that this different technique can reach sensitivity higher than 80%. In fact, in a work by Wei et al, they used ddPCR, and NGS for validation, and reached a higher sensitivity than in our work [15]. Similarly, Soria-Comes et al achieved a 70% sensitivity via qPCR [16].…”

“…Perhaps, EGFR mutations can be detectable in cfDNA when the tumor load is higher. In the work by Wei et al, they found the onset of T790M EGFR mutation during upfront TKI treatment and of C797S resistance EGFR mutation during second-line Osimertinib in liquid biopsy from four patients [15].…”

“…They found around 63% sensitivity and 83% specificity using a ddPCR assay for plasma samples. However, in their institution liquid biopsy was usually performed when tissue re-biopsy was not indicated because of clinical limitations [15]. In the paper by Soria-Comes et al, around 87% among 89 eligible patients had a result from liquid biopsy consistent with that from tissue biopsy.…”

Tissue Adequacy and Safety of Percutaneous Transthoracic Needle Biopsy for Molecular Analysis in Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis

“…For rebiopsies after chemotherapy, the adequacy rate of bronchoscopic biopsies for molecular analysis has been reported to be 73%–95% [ 45 46 47 48 49 50 ]. Recently, liquid biopsies, a set of methods that are used to enrich, detect, and analyze circulating tumor cells in cancer patients, have been used to diagnose and predict the prognosis of NSCLC patients [ 51 52 53 ]. Nevertheless, a comprehensive understanding of the comparative performance of various diagnostic methods for rebiopsies after chemotherapy is lacking.…”

Long-Term Survival of Over 6 Years with Afatinib Sequential Treatment in a Patient with EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Case Report

“…Despite the T790M-negative pleural biopsy, which could potentially have been caused by a false-negative EGFR test or an inadequate re-biopsied specimen for testing, the failure of afatinib treatment may still be attributable to T790M substitution, as intratumoral genetic heterogeneity, including T790M expression, has been documented [27][28][29]. A recent study has also suggested that primary EGFR Del19 mutation, brain metastasis, and longer PFS with initial EGFR TKI treatment are associated with acquired T790M resistance [30]. In this regard, analysis of both tissue biopsies and blood samples has been suggested to improve identification of the T790M mutation [25,31].…”