Data from Detection of T790M, the Acquired Resistance <i>EGFR</i> Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses

• DOI: 10.1158/1078-0432.c.6523506
• Publication Date: 2023-04-01T09:41:33Z
• Authors: Tilak K. Sundaresan; Lecia V. Sequist; John V. Heymach; Gregory J. Riely; Pasi A. Jänne; Walter H. Koch; James P. Sullivan; Douglas B. Fox; Robert Maher; Alona Muzikansky; Andrew Webb; Hai T. Tran; Uma Giri; Martin Fleisher; Helena A. Yu; Wen Wei; Bruce E. Johnson; Thomas A. Barber; John R. Walsh; Jeffrey A. Engelman; Shannon L. Stott; Ravi Kapur; Shyamala Maheswaran; Mehmet Toner; Daniel A. Haber
• Keywords: T790M; Liquid biopsy; Concordance; Acquired resistance; Circulating tumor DNA

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The T790M gatekeeper mutation in the &lt;i&gt;EGFR&lt;/i&gt; is acquired by some &lt;i&gt;EGFR&lt;/i&gt;-mutant non–small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance available, noninvasive approaches detection will critical guide management.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis 40 patients with tumors progressing on TKI therapy. We compared genotype from tumor biopsies simultaneously collected circulating cells (CTC) and DNA (ctDNA).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; genotypes were successfully obtained 30 (75%) biopsies, 28 (70%) CTC samples, 32 (80%) ctDNA samples. resistance-associated was detected 47% 50% using each genotyping assays, concordance among them ranging 57% 74%. Although CTC- ctDNA-based unsuccessful 20% 30% cases, two assays together enabled all available blood sample, identified 14 (35%) whom concurrent biopsy negative or indeterminate.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Discordant between blood-based analyses may result technological differences, well sampling different populations. use complementary provide most complete assessment patient's cancer, which should be validated predicting response T790M-targeted inhibitors. &lt;i&gt;Clin Cancer Res; 22(5); 1103–10. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;