Approximately 60% of EGFR mutant non-small cell lung cancer (NSCLC) patients treated with first/second generation EGFR-TKIs will acquire resistance by the T790M mutation. Since osimertinib, a third generation EGFR-TKI, is active for NSCLC with T790M, re-biopsy to examine the T790M status at the disease progression is necessary to administer osimertinib adequately. T790M monitoring in patients receiving EGFR-TKIs by plasma ctDNA could give valuable clinical information.
Patients with advanced or post-operative recurrent NSCLC with the sensitive EGFR mutations who receive the first EGFR-TKI treatment are eligible. Plasma samples at the baseline and the several timings of the disease are analyzed for EGFR mutation status using Cobas EGFR Mutation Test®.
Between September 2016 and March 2017, 122 patients at 15 institutions in Japan were enrolled. Total 1291 plasma samples from 121 patients were analyzed for EGFR mutation status at March 2018. At the baseline, the sensitive EGFR mutation (Ex19 del 14, L858R 15) was detected in 29 (23.9%) of 121 patients and the resistant EGFR mutation T790M was detected in 3 (2.5%) patients. During the follow up period, 63 (52.1%) patients experienced disease progression and 62 (51.2%) stopped the first EGFR-TKI treatment. Twenty-one (17.5%) patients showed T790M in plasma ctDNA. Median time from the first EGFR-TKI treatment to the detection of T790M in plasma ctDNA was 441 days. Although 30 patients received re-biopsy to examine the EGFR mutation status at the disease progression, T790M was detected in only eight (22.2%) of the 36 re-biopsied materials. Seven (87.5%) of the eight patients who showed T790M in the re-biopsied materials received osimertinib, whereas 12 (57.1%) of the 21 patients with T790M detection in plasma received osimertinib, 4 (19.0%) continued the first EGFR-TKI, and 4 (19.0%) received platinum-based chemotherapy.
Although ctDNA monitoring during the EGFR-TKI treatment is useful, further investigation is necessary to elucidate the efficacy of osimertinib treatment based on the T790M detection in plasma ctDNA.
Clinical trial identification
Legal entity responsible for the study
Y. Takeda: Grant/research funding: Taiho, Chugai, Kyowa Hakko Kirin, Boehringer Ingelheim. K. Uemura: Advisory: Ono, Zeria. Y. Ohashi: Executive compensation: Statcom; Honorarium for lecture: Sanofi, Eisai; Consultation: Chugai, Taiho, Kowa; Compensation for IDMC: Shionogi; Travel expense: Yakult, Takeda; Honorarium: Public Health Research Foundation, Daiichi-Sankyo. H. Kunitoh: Honorarium: AstraZeneca. All other authors have declared no conflicts of interest.