PMID- 35181499
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220603
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 17
IP  - 5
DP  - 2022 May
TI  - Osimertinib Plus Durvalumab in Patients With EGFR-Mutated, Advanced NSCLC: A 
      Phase 1b, Open-Label, Multicenter Trial.
PG  - 718-723
LID - S1556-0864(22)00081-8 [pii]
LID - 10.1016/j.jtho.2022.01.012 [doi]
AB  - INTRODUCTION: EGFR 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). METHODS: This 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. 
      RESULTS: Before 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). CONCLUSIONS: This 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.
CI  - Copyright (c) 2022 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Ahn, Myung-Ju
AU  - Ahn MJ
AD  - Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of 
      Medicine, Seoul, South Korea. Electronic address: silk.ahn@samsung.com.
FAU - Cho, Byoung Chul
AU  - Cho BC
AD  - Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Ou, Xiaoling
AU  - Ou X
AD  - Early Clinical Development, AstraZeneca, Cambridge, United Kingdom.
FAU - Walding, Andrew
AU  - Walding A
AD  - Late Development Oncology, AstraZeneca, Cambridge, United Kingdom.
FAU - Dymond, Angela W
AU  - Dymond AW
AD  - Covance Clinical Research Unit Limited, Leeds, United Kingdom.
FAU - Ren, Song
AU  - Ren S
AD  - Clinical Pharmacology & Quantitative Pharmacology, AstraZeneca, Gaithersburg, 
      Maryland.
FAU - Cantarini, Mireille
AU  - Cantarini M
AD  - Oncology R&D, AstraZeneca, Macclesfield, United Kingdom.
FAU - Janne, Pasi A
AU  - Janne PA
AD  - Lowe Center for Thoracic Oncology, Robert and Renee Belfer Center for Applied 
      Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
LA  - eng
SI  - ClinicalTrials.gov/NCT02143466
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20220215
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Acrylamides)
RN  - 0 (Aniline Compounds)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 28X28X9OKV (durvalumab)
RN  - 3C06JJ0Z2O (osimertinib)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Acrylamides
MH  - Aniline Compounds/pharmacology/therapeutic use
MH  - Antibodies, Monoclonal
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/metabolism
MH  - ErbB Receptors/genetics
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/metabolism
MH  - Mutation
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - Durvalumab
OT  - EGFR
OT  - NSCLC
OT  - Osimertinib
EDAT- 2022/02/20 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/02/19 05:28
PHST- 2021/11/02 00:00 [received]
PHST- 2022/01/12 00:00 [revised]
PHST- 2022/01/13 00:00 [accepted]
PHST- 2022/02/20 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/02/19 05:28 [entrez]
AID - S1556-0864(22)00081-8 [pii]
AID - 10.1016/j.jtho.2022.01.012 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2022 May;17(5):718-723. doi: 10.1016/j.jtho.2022.01.012. Epub 
      2022 Feb 15.