本期胸小星将为大家带来放化疗后奥希替尼治疗Ⅲ期EGFR突变的非小细胞肺癌；临床验证一项能增强肺癌早期诊断能力的细胞游离DNA片段检测，一起来看看吧！
2017·EATTS
01
Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC
Shun Lu1, Terufumi Kato1, Xiaorong Dong1, Myung-Ju Ahn1, Le-Van Quang1, Nopadol Soparattanapaisarn1, Takako Inoue1，Chih-Liang Wang1, Meijuan Huang1, James Chih-Hsin Yang1, Manuel Cobo1，Mustafa Özgüroğlu1, Ignacio Casarini1, Dang-Van Khiem1, Virote Sriuranpong1, Eduardo Cronemberger, Toshiaki Takahashi1, Yotsawaj Runglodvatana1, Ming Chen1, Xiangning Huang1, Ellie Grainger1, Dana Ghiorghiu1, Toon van der Gronde1, Suresh S. Ramalingam1; LAURA Trial Investigators
1 From the Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (S.L.), the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (X.D.), the Division of Thoracic Tumor Multimodality Treatment and Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (M.H.), the Department of Radiotherapy, the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), the Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou (M. Chen) - all in China; the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.), the Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka (T.I.), and the Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka (T.T.) - all in Japan; the Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (M.-J.A.); the Department of Oncology, Hanoi Medical University (L.-V.Q.), and the Department of Oncology, Vietnam National Lung Hospital (D.-V.K.) - both in Hanoi; the Faculty of Medicine, Siriraj Hospital, Mahidol University (N.S.), the Division of Medical Oncology, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital (V.S.), and the Faculty of Medicine, Vajira Hospital, Navamindradhiraj University (Y.R.) - all in Bangkok, Thailand; the Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, Medical College of Chang Gung University, Taoyuan (C.-L.W.), and the Department of Oncology, National Taiwan University Hospital, and the National Taiwan University Cancer Center, Taipei (J.C.-H.Y.) - all in Taiwan; Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Málaga, Spain (M. Cobo); the Department of Internal Medicine, Division of Medical Oncology, Clinical Trial Unit, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey (M.Ö.); Servicio Oncología, Hospital Bernardo Houssay, Mar del Plata, Buenos Aires (I.C.); Centro de Pesquisa Clínica, Centro Regional Integrado de Oncologia, Fortaleza, Brazil (E.C.); Biometrics, Late-Stage Development, Oncology Research and Development, AstraZeneca, Cambridge, United Kingdom (X.H., E.G.); Late-Stage Development, Oncology Research and Development, AstraZeneca, Baar, Switzerland (D.G.); Late-Stage Development, Oncology Research and Development, AstraZeneca, New York (T.G.); and the Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.).
Background:
Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR-tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC.
Methods:
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review.
Results:
A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P < 0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged.
Conclusion:
Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC.
[CITATION]: Lu S, Kato T, Dong X, et al. Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC. N Engl J Med. 2024 Jun 2.
[DOl]:10.1056/NEJMoa2402614
[IF]:158.5
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放化疗后奥希替尼治疗Ⅲ期EGFR突变的非小细胞肺癌
胸“星”外科学术团队兴趣小队成员 李金芳 译
背景
方法
结果
结论
Figure 1. Progression-free Survival According to Blinded Independent Central Review.
Table 3. Most Common Adverse Events of Any Cause in >5% of Patients in Either Group.
2017·EATTS
02
Clinical Validation of a Cell-free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection
Peter J. Mazzone1, Peter B. Bach2, Jacob Carey2, Caitlin A. Schonewolf2, Katalin Bognar3, Manmeet S. Ahluwalia4, Marcia Cruz-Correa5, David Gierada6, Sonali Kotagiri2, Kathryn Lloyd7, Fabien Maldonado8, Jesse D. Ortendahl9, Lecia V. Sequist10, Gerard A. Silvestri11, Nichole Tanner12, Jeffrey C. Thompson13, Anil Vachani13, Kwok-Kin Wong14, Ali H. Zaidi15, Joseph Catallini2, Ariel Gershman2, Keith Lumbard2, Laurel K. Millberg2, Jeff Nawrocki2, Carter Portwood2, Aakanksha Rangnekar2, Carolina Campos Sheridan2, Niti Trivedi2, Tony Wu2, Yuhua Zong2, Lindsey Cotton2, Allison Ryan2, Christopher Cisar2, Alessandro Leal2, Nicholas Dracopoli2, Robert B. Scharpf16, Victor E. Velculescu16*, Luke R. G. Pike17
1 Cleveland Clinic, Cleveland, Ohio, USA
2 DELFI Diagnostics, Baltimore, MD, USA
3 Medicus Economics, LLC; Formerly PHAR, San Francisco, CA, USA
4 Miami Cancer Institute, Baptist Health South Florida, Miami, FL
5 Pan American Center for Oncology, Puerto Rico
6 Washington University at St. Louis, St. Louis, MO, USA
7 Centura Health, Aurora, CO, USA
8 Vanderbilt Health, Nashville, TN, USA
9 Stratevi; Formerly PHAR, San Francisco, CA, USA
10 Massachusetts General Hospital, Boston, MA, USA
11 Medical University of South Carolina, Charleston, SC, USA
12 Department of Veterans Affairs, Charleston, SC, USA
13 Division of Pulmonary, Allergy and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
14 New York University Langone Health, New York, NY, USA
15 Allegheny Health Network
16 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
17 Memorial Sloan Kettering Cancer Center, New York, NY, USA
Objective:
Lung cancer screening via annual low-dose computed tomography (LDCT) has poor adoption.
Methods:
We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by an LDCT. Changes in genome-wide cell-free DNA (cfDNA) fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples, and then validated it in a held-out group of 382 cases and controls.
Results:
The validation demonstrated high sensitivity for lung cancer, and consistency across demographic groups and comorbid conditions.
Conclusion:
Applying test performance to the screening eligible population in a five-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.
[CITATION]: Mazzone PJ, Bach PB, Carey J, et al. Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection. Cancer Discov. 2024 Jun 3.
[DOI]: 10.1158/2159-8290.CD-24-0519
[IF]: 29.1
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临床验证一项能增强肺癌早期诊断能力的细胞游离DNA片段检测
胸“星”外科学术团队兴趣小队成员 李佳泽 译
目的
方法
结果
结论
Figure 4. Performance of blood-based lung cancer screening test.
Figure 4. Performance of blood-based lung cancer screening test.
2017·EATTS
