Thomas John1, Hiroaki Akamatsu2, Angelo Delmonte3, Wu-Chou Su4, Jong Seok Lee5, Gee-Chen Chang6, Xiangning Huang7, Suzanne Jenkins8, Yi-Long Wu9. 1. Department of Medical Oncology, Austin Health, Melbourne, Australia. Electronic address: Tom.John@onjcri.org.au. 2. Third department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address: h-akamat@wakayama-med.ac.jp. 3. Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy. Electronic address: angelo.delmonte@irst.emr.it. 4. Department of Internal Medicine, National Cheng Kung University Hospital, Taiwan, Taiwan. Electronic address: sunnysu@mail.ncku.edu.tw. 5. Department of Internal Medicine, Seoul National University, Bundang Hospital, Seongnam, Republic of Korea. Electronic address: jslee0918@gmail.com. 6. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, and Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: august@vghtc.gov.tw. 7. Biometrics and Informatics, GMD, AstraZeneca, Cambridge, UK. Electronic address: Xiangning.Huang@astrazeneca.com. 8. Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, UK. Electronic address: suzanne.jenkins@astrazeneca.com. 9. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn.
Abstract
OBJECTIVES: In AURA3 (NCT02151981), osimertinib treatment provided significant clinical benefit compared with platinum-pemetrexed in patients with epidermal growth factor receptor (EGFR) T790M-positive advanced non-small-cell lung cancer (NSCLC), whose tumors had progressed on previous EGFR-tyrosine kinase inhibitor therapy. This retrospective analysis investigated detection rates for T790M, common (exon 19 deletion and L858R), and rare EGFR mutations in tissue samples from the screened population of AURA3. MATERIALS AND METHODS: In AURA3, eligible patients were randomized 2:1 to receive oral osimertinib 80 mg once daily or intravenous platinum-pemetrexed every 3 weeks for up to six cycles. Tumor tissue samples were centrally tested for EGFR mutations using the cobas® EGFR Mutation Test (Version 2). T790M-positive status was a key inclusion criteria. RESULTS: A total of 820 screened patients had a valid EGFR mutation test result, of whom 452 (55%) were T790M-positive. Detection rates were similar by ethnicity (Asian versus non-Asian) for T790M (53% versus 58%) and exon 19 deletions (56% versus 63%). Conversely, the L858R rate was higher among Asian patients versus non-Asian patients (39% versus 28%; p = 0.0017). In the overall population, a higher proportion of patients had T790M detected against a background of exon 19 deletion versus L858R mutations (64% versus 47%; p < 0.0001). Rare EGFR mutations were detected in 28 (3%) patients, including G719X (2%), exon 20 insertion (1%), and S768I (<1%). CONCLUSION: Among AURA3 screened patients with EGFR mutation-positive advanced NSCLC, approximately half had detectable T790M in their tumor tissue, a rate unaffected by ethnicity. Results are consistent with previous reports of T790M detection rate in this patient population.
OBJECTIVES: In AURA3 (NCT02151981), osimertinib treatment provided significant clinical benefit compared with platinum-pemetrexed in patients with epidermal growth factor receptor (EGFR) T790M-positive advanced non-small-cell lung cancer (NSCLC), whose tumors had progressed on previous EGFR-tyrosine kinase inhibitor therapy. This retrospective analysis investigated detection rates for T790M, common (exon 19 deletion and L858R), and rare EGFR mutations in tissue samples from the screened population of AURA3. MATERIALS AND METHODS: In AURA3, eligible patients were randomized 2:1 to receive oral osimertinib 80 mg once daily or intravenous platinum-pemetrexed every 3 weeks for up to six cycles. Tumor tissue samples were centrally tested for EGFR mutations using the cobas® EGFR Mutation Test (Version 2). T790M-positive status was a key inclusion criteria. RESULTS: A total of 820 screened patients had a valid EGFR mutation test result, of whom 452 (55%) were T790M-positive. Detection rates were similar by ethnicity (Asian versus non-Asian) for T790M (53% versus 58%) and exon 19 deletions (56% versus 63%). Conversely, the L858R rate was higher among Asian patients versus non-Asian patients (39% versus 28%; p = 0.0017). In the overall population, a higher proportion of patients had T790M detected against a background of exon 19 deletion versus L858R mutations (64% versus 47%; p < 0.0001). Rare EGFR mutations were detected in 28 (3%) patients, including G719X (2%), exon 20 insertion (1%), and S768I (<1%). CONCLUSION: Among AURA3 screened patients with EGFR mutation-positive advanced NSCLC, approximately half had detectable T790M in their tumor tissue, a rate unaffected by ethnicity. Results are consistent with previous reports of T790M detection rate in this patient population.