Vassiliki A Papadimitrakopoulou1, Ji-Youn Han2, Myung-Ju Ahn3, Suresh S Ramalingam4, Angelo Delmonte5, Te-Chun Hsia6, Janessa Laskin7, Sang-We Kim8, Yong He9, Chun-Ming Tsai10, Toyoaki Hida11, Makoto Maemondo12, Terufumi Kato13, Suzanne Jenkins14, Sabina Patel14, Xiangning Huang14, Gianluca Laus15, Aleksandra Markovets16, Kenneth S Thress17, Yi-Long Wu18, Tony Mok19. 1. The University of Texas MD Anderson Cancer Center, Houston, Texas. 2. Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea. 3. Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea. 4. Winship Cancer Institute, Emory University, Atlanta, Georgia. 5. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. China Medical University, Taichung City, Taiwan. 7. British Columbia Cancer Agency, Vancouver, British Columbia, Canada. 8. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 9. Daping Hospital, Third Military Medical University, Chongqing, China. 10. Taipei Veterans General Hospital, Taipei, Taiwan. 11. Aichi Cancer Center, Nagoya, Japan. 12. Iwate Medical University School of Medicine, Iwate, Japan. 13. Kanagawa Cancer Center, Yokohama, Japan. 14. Precision Medicine, R&D Oncology, AstraZeneca, Cambridge, United Kingdom. 15. Global Medicines Development, AstraZeneca, Cambridge, United Kingdom. 16. Translational Medicine, Oncology, AstraZeneca, Boston, Massachusetts. 17. Oncology Translational Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Waltham, Massachusetts. 18. Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. 19. State Key Laboratory of South China, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.
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.
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.
Authors: Pei N Ding; Tara L Roberts; Wei Chua; Therese M Becker; Nicole Caixeiro; Paul de Souza; Bo Gao; Chee K Lee; Malinda Itchins; Helen Westman; Stephen Clarke; Prunella Blinman; Steven Kao; Tom John; Jose L Leal; Victoria J Bray Journal: Transl Lung Cancer Res Date: 2021-04
Authors: Jill F Mentink; Marthe S Paats; Daphne W Dumoulin; Robin Cornelissen; Joris B W Elbers; Alexander P W M Maat; Jan H von der Thüsen; Anne-Marie C Dingemans Journal: Transl Lung Cancer Res Date: 2021-07
Authors: Catherine B Meador; Marina S D Milan; Emmy Y Hu; Mark M Awad; Michael S Rabin; Cloud P Paweletz; Ryan Hartmaier; Gianluca Laus; Geoffrey R Oxnard Journal: JCO Precis Oncol Date: 2021-06-01