Epidermal growth factor receptor mutation analysis in tissue and plasma from the AURA3 trial: Osimertinib versus platinum-pemetrexed for T790M mutation-positive advanced non-small cell lung cancer
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, Tony Mok, 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, Tony Mok
Abstract
Background: This 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.
Methods: Tumor 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).
Results: With 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).
Conclusions: PPA 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.
Keywords: AURA3; T790M; circulating tumor DNA (ctDNA); epidermal growth factor receptor (EGFR) mutation; epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI); non-small cell lung cancer (NSCLC); osimertinib; plasma; tissue.
© 2019 American Cancer Society.
References
- Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4:1046-1061.
- Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629-640.
- Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113-125.
- European Medicines Agency. Tagrisso (Osimertinib): Summary of Product Characteristics. Accessed February 22, 2019.
- US Food and Drug Administration. Tagrisso (Osimertinib): Highlights of Prescribing Information. Accessed April 26, 2018.
- Goldman JW, Noor ZS, Remon J, Besse B, Rosenfeld N. Are liquid biopsies a surrogate for tissue EGFR testing? Ann Oncol. 2018;29:i38-i46.
- Jenkins S, Yang JC, Ramalingam SS, et al. Plasma ctDNA analysis for detection of the EGFR T790M mutation in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2017;12:1061-1070.
- Mellert H, Foreman T, Jackson L, et al. Development and clinical utility of a blood-based test service for the rapid identification of actionable mutations in non-small cell lung carcinoma. J Mol Diagn. 2017;19:404-416.
- Hu Y, Alden RS, Odegaard JI, et al. Discrimination of germline EGFR T790M mutations in plasma cell-free DNA allows study of prevalence across 31,414 cancer patients. Clin Cancer Res. 2017;23:7351-7359.
- US Food and Drug Administration. Premarket approval P120019 for Cobas EGFR Mutation Test v2. Accessed August 29, 2019. .
- Jenkins S, Chih-Hsin Yang J, Janne PA, et al. EGFR mutation analysis for prospective patient selection in two phase II registration studies of osimertinib. J Thorac Oncol. 2017;12:1247-1256.
- Thress KS, Brant R, Carr TH, et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: a cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015;90:509-515.
- Bordi P, Del Re M, Minari R, et al. From the beginning to resistance: study of plasma monitoring and resistance mechanisms in a cohort of patients treated with osimertinib for advanced T790M-positive NSCLC. Lung Cancer. 2019;131:78-85.
- Labbe C, Cabanero M, Korpanty GJ, et al. Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Lung Cancer. 2017;111:23-29.
- Camidge D, Pao W, Sequist L. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol. 2014;11:473-481.
Source: PubMed