Sequential Afatinib and Osimertinib in Asian Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer and Acquired T790M: Combined Analysis of Two Global Non-Interventional Studies

Abstract

Satoru Miura,1 Hyun Ae Jung,2 Shin Yup Lee,3 Seung Hyeun Lee,4 Min Ki Lee,5 Yong Chul Lee,6 Maximilian J Hochmair,7 Cheng-Ta Yang,8 Angela Märten,9 James Chih-Hsin Yang,10 Sanjay Popat11,12 1Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, South Korea; 5Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea; 6Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea; 7Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Vienna, Austria; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 10Department of Medical Oncology, National Taiwan University Cancer Center and Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 11Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; 12The Institute of Cancer Research, London, United KingdomCorrespondence: Sanjay Popat, Lung Unit, Royal Marsden National Health Service Foundation Trust, 203 Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom, Tel [phone], Email [email protected]: Two recent non-interventional trials, GioTag and UpSwinG, demonstrated encouraging time-to-treatment failure (TTF) and overall survival (OS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Del19 or L858R) who received sequential afatinib/osimertinib, especially in Asians. Here, we have undertaken a combined analysis of Asian patients from both studies.Materials and Methods: Existing medical/electronic records were identified for consecutive EGFR-tyrosine kinase inhibitor (TKI)-naïve patients who received first-line afatinib/second-line osimertinib in “real-world” practice (all T790M-positive). Patients with active brain metastases were excluded. The primary objective was TTF. OS was a key secondary objective.Results: One hundred and sixty-eight patients were analyzed. Most patients were recruited from South Korea or Japan (52/21%). At the start of afatinib, median age (range) was 61.5 years (35– 88), 58% were female, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0/1/≥ 2) was 29/62/9%, 17% had brain metastases, and EGFR mutation status (Del19/L858R) was 65/35%. At the start of osimertinib, ECOG PS (0/1/≥ 2) was 22/61/17% and 14% had brain metastases. Median TTF and OS were 30.0 months (95% CI: 24.5– 32.5) and 45.2 months (95% CI: 41.7– 71.1), respectively. Median OS was 63.5 months in patients with a Del19 mutation. Median OS in patients with brain metastases or ECOG PS ≥ 2 was 26.4 and 33.1 months, respectively.Conclusion: Sequential afatinib/osimertinib showed encouraging activity in Asian patients with EGFR mutation-positive NSCLC and T790M-mediated acquired resistance, especially those with Del19-positive disease. Activity was observed across “real-world” patients including those with poor ECOG PS and/or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib.Graphical Abstract: Keywords: EGFR, afatinib, osimertinib, sequential, T790M

Keywords

• egfr
• afatinib
• osimertinib
• sequential
• t790m