Sanjay Popat1, Hyun Ae Jung2, Shin Yup Lee3, Maximilian J Hochmair4, Seung Hyeun Lee5, Carles Escriu6, Min Ki Lee7, Maria R Migliorino8, Yong Chul Lee9, Nicolas Girard10, Hasan Daoud11, Angela Märten12, Satoru Miura13. 1. Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom. Electronic address: Sanjay.Popat@rmh.nhs.uk. 2. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: hyunae.jung@samsung.com. 3. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea. Electronic address: shinyup@knu.ac.kr. 4. Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria. Electronic address: hausruck@gmail.com. 5. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Dongdaemun-gu, Seoul, South Korea. Electronic address: humanmd04@hanmail.net. 6. The Clatterbridge Cancer Centre, Bebington, Wirral, United Kingdom. Electronic address: Carles.escriu@nhs.net. 7. Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea. Electronic address: leemk@pusan.ac.kr. 8. San Camillo-Forlanini Hospital, Rome, Italy. Electronic address: mmigliorino@scamilloforlanini.rm.it. 9. Department of Internal Medicine, Research Center for Pulmonary Disease, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, South Korea. Electronic address: leeyc@chonbuk.ac.kr. 10. Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France and UVSQ, Paris Saclay, Saint Aubin, France. Electronic address: nicolas.girard2@curie.fr. 11. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. Electronic address: hasan.daoud@boehringer-ingelheim.com. 12. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. Electronic address: angela.maerten@boehringer-ingelheim.com. 13. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. Electronic address: miusat1118@niigata-cc.jp.
Abstract
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance. METHODS: In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR). RESULTS: At the start of afatinib treatment, median age (range) was 62 years (34-88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0-30.2) and median OS was 36.5 months (95% CI: 32.9-41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups. CONCLUSION: Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment.
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance. METHODS: In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR). RESULTS: At the start of afatinib treatment, median age (range) was 62 years (34-88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0-30.2) and median OS was 36.5 months (95% CI: 32.9-41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups. CONCLUSION: Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment.
Authors: Wang Chun Kwok; James Chung Man Ho; Terence Chi Chun Tam; Mary Sau Man Ip; David Chi Leung Lam Journal: Thorac Cancer Date: 2022-06-06 Impact factor: 3.223