Abstract 56P
Background
T790M testing is recommended after resistance to first or second-generation EGFR tyrosine kinase inhibitors (TKIs). However, the role of simultaneous tissue and liquid next-generation sequencing (NGS) after first-line EGFR TKI resistance is still unclear.
Methods
We prospectively analyzed lung cancer patients’ cancer tissues and corresponding cell-free DNA (cfDNA) after first-line EGFR TKI progression by targeted NGS, ACTDrug® + and ACTMonitor® Lung. Patients’ clinicopathologic characteristics and treatment outcomes were analyzed.
Results
Total 86 patients received tissue rebiopsy and cfDNA analysis for NGS study. 26 of them did not have adequate tissue for NGS, but 5 T790M was found in their cfDNA. Finally, there were 60 patients with paired tissue and cfDNA NGS. 15 received gefitinib, 27 received erlotinib, 16 received afatinib and 2 received osimertinib as the first-line therapy. The concordance rates between tissue and cfDNA were 87% for exon 19 deletion, 78% for L858R and 68% for T790M, respectively. Among the 58 patients receiving gefitinib, erlotinib or afatinib, T790M were found in 29 (50%) patients, with 5 (17%) of them had T790M detected only in cfDNA. 24 patients were subsequently treated with osimertinib and the progression-free survival (PFS) and OS were longer in patients without detectable variant from cfDNA than patients with variants detected from cfDNA (p=0.049 and p=0.02 respectively). Among the other 29 patients without T790M, ERBB2 copy number gain (CNG) was found in 4, MET CNG was found in 5 and EGFR CNG was found in 5. One patient with MET CNG kept erlotinib and added-on capmatinib. Partial response achieved, with a PFS of 12.4 months. For patients received first-line osimertinib, one had CCDC6-RET fusion and EGFR CNG. The other had MET CNG and EGFR CNG. However, they did not receive any RET or MET inhibitors as their sequential treatments.
Conclusions
NGS at EGFR TKI progression provides more information for sequential anticancer therapy. Simultaneous tissue NGS and cfDNA NGS may help to identify more T790M patients. Non-detectable variant in cfDNA NGS might predict better outcome in T790M-positive patients.
Legal entity responsible for the study
The authors.
Funding
ACT Genomics.
Disclosure
Y. Lin: Financial Interests, Personal, Invited Speaker: ACT Genomics; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Manudipharma; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker, and Travel Expense: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: TTY Biopharm. W. Liao: Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: MSD Oncology; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, and Speaker’s Bureau: Chugai Pharma Taiwan. K.T. Tan: Financial Interests, Personal, Full or part-time Employment: ACT Genomics. W. Hsiao: Financial Interests, Personal, Full or part-time Employment: ACT Genomics. J. Shih: Financial Interests, Personal, Advisory Board, and Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board, and Invited Speaker and Grant: Roche; Financial Interests, Personal, Advisory Board, and Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, and Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board, and Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board, and Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board, and Invited Speaker: MSD; Financial Interests, Personal, Advisory Board, and Invited Speaker: Chugai Pharma; Financial Interests, Personal, Advisory Board, and Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: CStone Pharmaceuticals; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker, and Invited Speaker: Bristol Myers Squibb. All other authors have declared no conflicts of interest.