• Vassiliki A Papadimitrakopoulou, Ji-Youn Han, Myung-Ju Ahn, Suresh S Ramalingam, Angelo Delmonte, Te-Chun Hsia, Janessa Laskin, Sang-We Kim, Yong He, Chun-Ming Tsai, Toyoaki Hida, Makoto Maemondo, Terufumi Kato, Suzanne Jenkins, Sabina Patel, Xiangning Huang, Gianluca Laus, Aleksandra Markovets, Kenneth S Thress, Yi-Long Wu, and Tony Mok.
• The University of Texas MD Anderson Cancer Center, Houston, Texas.
• Cancer. 2020 Jan 15; 126 (2): 373-380.

BackgroundThis study assesses different technologies for detecting epidermal growth factor receptor (EGFR) mutations from circulating tumor DNA in patients with EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) from the AURA3 study (NCT02151981), and it evaluates clinical responses to osimertinib and platinum-pemetrexed according to the plasma T790M status.MethodsTumor tissue biopsy samples were tested for T790M during screening with the cobas EGFR Mutation Test (cobas tissue). Plasma samples were collected at screening and at the baseline and were retrospectively analyzed for EGFR mutations with the cobas EGFR Mutation Test v2 (cobas plasma), droplet digital polymerase chain reaction (ddPCR; Biodesix), and next-generation sequencing (NGS; Guardant360, Guardant Health).ResultsWith cobas tissue test results as a reference, the plasma T790M positive percent agreement (PPA) was 51% (110 of 215 samples) by cobas plasma, 58% (110 of 189) by ddPCR, and 66% (136 of 207) by NGS. Plasma T790M detection was associated with a larger median baseline tumor size (56 mm for T790M-positive vs 39 mm for T790M-negative; P < .0001) and the presence of extrathoracic disease (58% for M1b-positive vs 39% for M0-1a-positive; P = .002). Progression-free survival (PFS) was prolonged in randomized patients (tissue T790M-positive) with a T790M-negative cobas plasma result in comparison with those with a T790M-positive plasma result in both osimertinib (median, 12.5 vs 8.3 months) and platinum-pemetrexed groups (median, 5.6 vs 4.2 months).ConclusionsPPA was similar between ddPCR and NGS assays; both were more sensitive than cobas plasma. All 3 test platforms are suitable for routine clinical practice. In patients with tissue T790M-positive NSCLC, an absence of detectable plasma T790M at the baseline is associated with longer PFS, which may be attributed to a lower disease burden.© 2019 American Cancer Society.

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