Suzanne Jenkins1, James C-H Yang2, Suresh S Ramalingam3, Karen Yu4, Sabina Patel5, Susie Weston6, Rachel Hodge5, Mireille Cantarini6, Pasi A Jänne7, Tetsuya Mitsudomi8, Glenwood D Goss9. 1. AstraZeneca, Alderley Park, United Kingdom. Electronic address: Suzanne.Jenkins@astrazeneca.com. 2. National Taiwan University Hospital, Taipei, Republic of China. 3. Emory University, Winship Cancer Institute, Atlanta, Georgia. 4. Roche Molecular Systems, Inc., Pleasanton, California. 5. AstraZeneca, Cambridge, United Kingdom. 6. AstraZeneca, Alderley Park, United Kingdom. 7. Dana-Farber Cancer Institute, Boston, Massachusetts. 8. Kindai University Faculty of Medicine, Osaka-Sayama, Japan. 9. Ottawa Hospital Research Institute, Centre for Cancer Therapeutics, Ottawa, Canada.
Abstract
INTRODUCTION: Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment. METHODS: Matched tumor tissue and plasma samples from patients screened for the AURA extension and AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma-based cobas EGFR mutation tests. Plasma test performance was assessed by using the cobas tissue test and a next-generation sequencing method (MiSeq [Illumina Inc., San Diego, CA]) as references. The objective response rate, measured by blinded independent central review, was assessed in patients receiving osimertinib with a plasma T790M mutation-positive status. RESULTS: During screening, 551 patients provided matched tumor tissue and plasma samples. Pooled analysis of the positive and negative percent agreements between the cobas plasma and tissue tests for detection of T790M mutation were 61% and 79%, respectively. Comparing cobas plasma test with next-generation sequencing demonstrated positive and negative percent agreements of 90% or higher. The objective response rate was 64% (95% confidence interval: 57-70) in T790M mutation-positive patients by both cobas tissue and plasma tests (evaluable for response). CONCLUSIONS: The cobas plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation-positive patients. To mitigate the risk of false-negative plasma results, patients with a negative plasma result should undergo a tissue test where feasible.
INTRODUCTION:Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment. METHODS: Matched tumor tissue and plasma samples from patients screened for the AURA extension and AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma-based cobas EGFR mutation tests. Plasma test performance was assessed by using the cobas tissue test and a next-generation sequencing method (MiSeq [Illumina Inc., San Diego, CA]) as references. The objective response rate, measured by blinded independent central review, was assessed in patients receiving osimertinib with a plasma T790M mutation-positive status. RESULTS: During screening, 551 patients provided matched tumor tissue and plasma samples. Pooled analysis of the positive and negative percent agreements between the cobas plasma and tissue tests for detection of T790M mutation were 61% and 79%, respectively. Comparing cobas plasma test with next-generation sequencing demonstrated positive and negative percent agreements of 90% or higher. The objective response rate was 64% (95% confidence interval: 57-70) in T790M mutation-positive patients by both cobas tissue and plasma tests (evaluable for response). CONCLUSIONS: The cobas plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation-positive patients. To mitigate the risk of false-negative plasma results, patients with a negative plasma result should undergo a tissue test where feasible.
Authors: Charu Aggarwal; Christian D Rolfo; Geoffrey R Oxnard; Jhanelle E Gray; Lynette M Sholl; David R Gandara Journal: Nat Rev Clin Oncol Date: 2020-09-11 Impact factor: 66.675
Authors: Caroline E McCoach; Collin M Blakely; Kimberly C Banks; Benjamin Levy; Ben M Chue; Victoria M Raymond; Anh T Le; Christine E Lee; Joseph Diaz; Saiama N Waqar; William T Purcell; Dara L Aisner; Kurtis D Davies; Richard B Lanman; Alice T Shaw; Robert C Doebele Journal: Clin Cancer Res Date: 2018-03-29 Impact factor: 12.531