Detection and Dynamic Changes of <i>EGFR</i> Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy
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- Tony Mok
- 1State Key Laboratory of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong.
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- Yi-Long Wu
- 2Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
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- Jin Soo Lee
- 3National Cancer Center, Goyang, Korea.
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- Chong-Jen Yu
- 4National Taiwan University Hospital, Taipei, Taiwan.
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- Virote Sriuranpong
- 5The King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand.
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- Jennifer Sandoval-Tan
- 6Philippine General Hospital, Manila, Philippines.
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- Guia Ladrera
- 7Lung Centre of the Philippines, Quezon City, Philippines.
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- Sumitra Thongprasert
- 8Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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- Vichien Srimuninnimit
- 9Siriraj Hospital, Bangkok, Thailand.
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- Meilin Liao
- 10Shanghai Lung Tumour Clinical Medical Center, Shanghai Chest Hospital, Shanghai, China.
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- Yunzhong Zhu
- 11Beijing Chest Hospital, Beijing, China.
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- Caicun Zhou
- 12Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
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- Fatima Fuerte
- 13Rizal Medical Center, Pasig City, Philippines.
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- Benjamin Margono
- 14Dokter Soetomo Hospital, Surabaya, Indonesia.
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- Wei Wen
- 15Roche Molecular Systems, Inc., Pleasanton, California.
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- Julie Tsai
- 15Roche Molecular Systems, Inc., Pleasanton, California.
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- Matt Truman
- 16Roche Products Ltd, Dee Why, Australia.
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- Barbara Klughammer
- 17F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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- David S. Shames
- 18Oncology Biomarker Development, Genentech Inc., San Francisco, California.
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- Lin Wu
- 15Roche Molecular Systems, Inc., Pleasanton, California.
抄録
<jats:title>Abstract</jats:title> <jats:p>Purpose: Blood-based circulating-free (cf) tumor DNA may be an alternative to tissue-based EGFR mutation testing in NSCLC. This exploratory analysis compares matched tumor and blood samples from the FASTACT-2 study.</jats:p> <jats:p>Experimental Design: Patients were randomized to receive six cycles of gemcitabine/platinum plus sequential erlotinib or placebo. EGFR mutation testing was performed using the cobas tissue test and the cobas blood test (in development). Blood samples at baseline, cycle 3, and progression were assessed for blood test detection rate, sensitivity, and specificity; concordance with matched tumor analysis (n = 238), and correlation with progression-free survival (PFS) and overall survival (OS).</jats:p> <jats:p>Results: Concordance between tissue and blood tests was 88%, with blood test sensitivity of 75% and a specificity of 96%. Median PFS was 13.1 versus 6.0 months for erlotinib and placebo, respectively, for those with baseline EGFR mut+ cfDNA [HR, 0.22; 95% confidence intervals (CI), 0.14–0.33, P < 0.0001] and 6.2 versus 6.1 months, respectively, for the EGFR mut− cfDNA subgroup (HR, 0.83; 95% CI, 0.65–1.04, P = 0.1076). For patients with EGFR mut+ cfDNA at baseline, median PFS was 7.2 versus 12.0 months for cycle 3 EGFR mut+ cfDNA versus cycle 3 EGFR mut− patients, respectively (HR, 0.32; 95% CI, 0.21–0.48, P < 0.0001); median OS by cycle 3 status was 18.2 and 31.9 months, respectively (HR, 0.51; 95% CI, 0.31–0.84, P = 0.0066).</jats:p> <jats:p>Conclusions: Blood-based EGFR mutation analysis is relatively sensitive and highly specific. Dynamic changes in cfDNA EGFR mutation status relative to baseline may predict clinical outcomes. Clin Cancer Res; 21(14); 3196–203. ©2015 AACR.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 21 (14), 3196-3203, 2015-07-14
American Association for Cancer Research (AACR)