Osimertinib Plus Durvalumab in Patients With EGFR-Mutated,Advanced NSCLC: A Phase 1b,Open-Label,Multicenter Trial |
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| Affiliation: | 1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;2. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea;3. Early Clinical Development, AstraZeneca, Cambridge, United Kingdom;4. Late Development Oncology, AstraZeneca, Cambridge, United Kingdom;5. Covance Clinical Research Unit Limited, Leeds, United Kingdom;6. Clinical Pharmacology & Quantitative Pharmacology, AstraZeneca, Gaithersburg, Maryland;7. Oncology R&D, AstraZeneca, Macclesfield, United Kingdom;8. Lowe Center for Thoracic Oncology, Robert and Renée Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts;1. Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China;2. Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China;3. School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China;1. Department of Hematology-Oncology, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates;2. Department of Medical Oncology, Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore, Pakistan;3. Department of Oncology, Jinnah Hospital, Lahore, Pakistan;4. Department of Clinical and Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital & Research Center, Peshawar, Pakistan;1. Department of Oncology, McMaster University, Hamilton, Ontario, Canada;2. Department of Radiation Oncology, Medical University of South Carolina (MUSC), Charleston, South Carolina;3. Department of Cell and Molecular Pharmacology, Medical University of South Carolina (MUSC), Charleston, South Carolina;4. No Affiliation;1. School of Health & Biomedical Sciences, RMIT University, Bundoora, Australia;2. Department of Anatomical Pathology, St Vincent’s Hospital, Melbourne, Australia;3. Department of Respiratory Medicine & Sleep Medicine, Royal Melbourne Hospital, Melbourne, Australia;4. Department of Respiratory Medicine & Sleep Medicine, Austin Health, Heidelberg, Australia;5. The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;6. Faculty of Medicine, University of Melbourne, Parkville, Australia;1. Division of Thoracic Surgery, Department of Surgery, Yale University School of Medicine, Yale University, New Haven, Connecticut;2. Department of Immunobiology, Yale University School of Medicine, Yale University, New Haven, Connecticut |
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| Abstract: | IntroductionEGFR tyrosine kinase inhibitors (TKIs) are recommended for EGFR-mutated NSCLC treatment. EGFR activation up-regulates programmed death-ligand 1 expression and other immunosuppressive factors in NSCLC, causing immune microenvironment remodeling. Osimertinib (an EGFR TKI) plus durvalumab (programmed death-ligand 1 blockade) was evaluated in the TATTON study (NCT02143466).MethodsThis open-label, phase 1b study enrolled patients with advanced EGFR-mutated NSCLC. In part A, patients who had progressed on a previous EGFR TKI received osimertinib (80 mg once daily) plus durvalumab 3 or 10 mg/kg every 2 weeks. In part B, patients received first-line osimertinib plus durvalumab 10 mg/kg every 2 weeks. However, part B enrollment was terminated early owing to an increased incidence of interstitial lung disease (ILD)-related adverse events (AEs). Safety (primary objective) and preliminary anti-tumor activity determined by objective response rate (ORR), best overall response, duration of response (DOR), and progression-free survival were evaluated.ResultsBefore enrollment termination, 23 and 11 patients received treatment across parts A and B, respectively. The most common AEs across parts A and B were as follows: diarrhea (50%), nausea (41%), and decreased appetite (35%). A total of 12 patients (35%) reported ILD-related AEs (lung disorder, ILD or pneumonitis). In part A, ORR was 43% (95% confidence interval [CI]: 23–66); median DOR was 20.4 months. In part B, ORR was 82% (95% CI: 48–98), median DOR was 7.1 months, and median progression-free survival was 9.0 months (95% CI: 3.5–12.3).ConclusionsThis study highlighted a potential risk of ILD-related AEs when combining osimertinib with durvalumab. Further research looking to combine EGFR TKIs with immune checkpoint inhibitors should be approached with caution. |
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| Keywords: | NSCLC EGFR Osimertinib Durvalumab |
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