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

Satoru Miura; Hyun Ae Jung; Shin Yup Lee; Seung Hyeun Lee; Min Ki Lee; Yong Chul Lee; Maximilian J Hochmair; Cheng-Ta Yang; Angela Märten; James Chih-Hsin Yang; Sanjay Popat

doi:10.2147/OTT.S362535

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

Onco Targets Ther. 2022 Aug 22:15:873-882. doi: 10.2147/OTT.S362535. eCollection 2022.

Authors

Satoru Miura¹, Hyun Ae Jung², Shin Yup Lee³, Seung Hyeun Lee⁴, Min Ki Lee⁵, Yong Chul Lee⁶, Maximilian J Hochmair⁷, Cheng-Ta Yang⁸, Angela Märten⁹, James Chih-Hsin Yang¹⁰, Sanjay Popat^{11

12}

Affiliations

¹ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
² Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³ Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁴ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, South Korea.
⁵ Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea.
⁶ Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea.
⁷ Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Vienna, Austria.
⁸ Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁹ Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
¹⁰ Department of Medical Oncology, National Taiwan University Cancer Center and Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
¹¹ Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
¹² The Institute of Cancer Research, London, United Kingdom.

Abstract

Objective: 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.

Keywords: EGFR; T790M; afatinib; osimertinib; sequential.

Grants and funding

This study was funded by Boehringer Ingelheim. The sponsor played a role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication and, as such, are included in the author list. BI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. The authors received no direct compensation related to the development of the manuscript and met criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).