PMID- 34307179
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220425
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Afatinib in EGFR TKI-Naive Patients with Locally Advanced or Metastatic EGFR 
      Mutation-Positive Non-Small Cell Lung Cancer: A Pooled Analysis of Three Phase 
      IIIb Studies.
PG  - 709877
LID - 10.3389/fonc.2021.709877 [doi]
LID - 709877
AB  - BACKGROUND: Afatinib is approved for first-line treatment of patients with 
      epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung 
      cancer (NSCLC). Here, we report findings from a combined analysis of three phase 
      IIIb studies of afatinib in EGFR tyrosine kinase inhibitor (TKI)-naive patients. 
      METHODS: EGFR-TKI-naive patients with EGFRm+ NSCLC received afatinib 40 mg/day. 
      Dose reductions were permitted for adverse events (AEs). Efficacy endpoints 
      included progression-free survival (PFS), time to symptomatic progression (TTSP), 
      and tumor response. Subgroup analyses were performed by Eastern Cooperative 
      Oncology Group performance status (ECOG PS), presence of brain metastasis, age 
      and common/uncommon EGFR mutations (plus other factors). RESULTS: 1108 patients 
      were treated. Median age was 61 years (range, 25-89); 19.2% had baseline brain 
      metastases, 4.4% had ECOG PS >/=2, and 17.9% had tumors harboring uncommon 
      mutations. Treatment-related AEs (TRAEs) were reported in 97.2%, most commonly 
      diarrhea and rash. 41.6% had AEs leading to dose reduction. Median PFS was 13.0 
      months [95% confidence interval (CI): 12.0-13.8]; median TTSP was 14.8 months 
      (95% CI: 13.9-16.1). Objective response rate (ORR) was 55.0%. Age, presence of 
      baseline brain metastases, major (G719X, L861Q, S768I) or compound uncommon 
      mutations had little/no effect on PFS, TTSP, or ORR, while outcomes were poorer 
      in patients with ECOG PS 2 or exon 20 insertion/T790M mutations. CONCLUSIONS: 
      Afatinib was tolerable with no new safety signals. Afatinib demonstrated 
      encouraging efficacy in a broad patient population, including those with brain 
      metastases or uncommon EGFR mutations.
CI  - Copyright (c) 2021 Passaro, de Marinis, Tu, Laktionov, Feng, Poltoratskiy, Zhao, 
      Tan, Gottfried, Lee, Kowalski, Yang, Srinivasa, Clementi, Jalikop, Huang, Cseh, 
      Park and Wu.
FAU - Passaro, Antonio
AU  - Passaro A
AD  - Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, 
      Italy.
FAU - de Marinis, Filippo
AU  - de Marinis F
AD  - Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, 
      Italy.
FAU - Tu, Hai-Yan
AU  - Tu HY
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Laktionov, Konstantin K
AU  - Laktionov KK
AD  - Russian Academy of Medical Sciences, Moscow, Russia.
FAU - Feng, Jifeng
AU  - Feng J
AD  - Jiangsu Provincial Tumor Hospital, Nanjing, China.
FAU - Poltoratskiy, Artem
AU  - Poltoratskiy A
AD  - Petrov Research Institute of Oncology, St Petersburg, Russia.
FAU - Zhao, Jun
AU  - Zhao J
AD  - Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Tan, Eng Huat
AU  - Tan EH
AD  - National Cancer Centre, Singapore, Singapore.
FAU - Gottfried, Maya
AU  - Gottfried M
AD  - Tel Aviv University, Tel Aviv, Israel.
FAU - Lee, Victor
AU  - Lee V
AD  - Department of Clinical Oncology, Queen Mary Hospital, The University of Hong 
      Kong, Hong Kong, China.
FAU - Kowalski, Dariusz
AU  - Kowalski D
AD  - Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
FAU - Yang, Cheng Ta
AU  - Yang CT
AD  - Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan.
FAU - Srinivasa, B J
AU  - Srinivasa BJ
AD  - HCG Hospital, Bangalore, India.
FAU - Clementi, Laura
AU  - Clementi L
AD  - Boehringer Ingelheim Italia S.p.A., Milan, Italy.
FAU - Jalikop, Tejaswini
AU  - Jalikop T
AD  - Syneos Health, Raleigh, NC, United States.
FAU - Huang, Dennis Chin Lun
AU  - Huang DCL
AD  - Boehringer Ingelheim Taiwan Limited, Taipei, Taiwan.
FAU - Cseh, Agnieszka
AU  - Cseh A
AD  - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
FAU - Park, Keunchil
AU  - Park K
AD  - Division of Hematology Oncology, Samsung Medical Center Sungkyunkwan University 
      School of Medicine, Seoul, South Korea.
FAU - Wu, Yi-Long
AU  - Wu YL
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20210709
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8298067
OTO - NOTNLM
OT  - EGFR TKI-naive
OT  - EGFR mutation
OT  - NSCLC
OT  - afatinib
OT  - real world
OT  - safety
COIS- LC is an employee of Boehringer Ingelheim Italia S.p.A. TJ is an employee of 
      Syneos Health. DCLH is an employee of Boehringer Ingelheim Taiwan Limited. AC is 
      an employee of Boehringer Ingelheim International GmbH. APa received honoraria 
      for consulting, advisory role or lectures from AstraZeneca, Agilent/Dako, 
      Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Jansenn, Merck Sharp & 
      Dohme, Pfizer and Roche Genentech. FdM has received honoraria or consulting fees 
      from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Roche. KKL 
      reports receiving advisory council or committee fees from Boehringer-Ingelheim, 
      Bristol Myers Squibb, Merck Sharp & Dohme, Merck, Amgen, Roche, Takeda, Pfizer; 
      and grants or funds from Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp 
      & Dohme, Merck, Amgen, Roche, Takeda, Pfizer. VL reports receiving honoraria from 
      AstraZeneca, Eli Lilly, Novartis, Roche, Merck Sharp & Dohme. DK reports 
      receiving advisory council or committee fees from Boehringer Ingelheim, Bristol 
      Myers Squibb, Merck Sharp & Dohme, Merck, Amgen, Roche-Genentech, Takeda, Pfizer; 
      and consulting fees from Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp 
      & Dohme, Merck, Amgen, Roche-Genentech, Pfizer. KP reports receiving personal 
      fees from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi 
      Sankyo, Eli Lilly, Hanmi, Kyowa Hakko Kirin, Incyte, LOXO, Merck KGaA, Merck 
      Sharp & Dohme, Ono, Novartis, and Roche; and research funding from AstraZeneca 
      and Merck Sharp & Dohme. Y-LW reports receiving honoraria from AstraZeneca, 
      Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, 
      Pfizer, Sanofi, Roche; and grants/patents received or pending from AstraZeneca, 
      Boehringer Ingelheim, Bristol Myers Squibb. The remaining authors declare that 
      the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest. The 
      authors declare that this study received funding from Boehringer Ingelheim 
      International GmbH. The study sponsor participated in the design of the studies, 
      the collection, analysis, and interpretation of the data, writing this article, 
      and the decision to submit the article for publication.
EDAT- 2021/07/27 06:00
MHDA- 2021/07/27 06:01
PMCR- 2021/01/01
CRDT- 2021/07/26 06:37
PHST- 2021/05/14 00:00 [received]
PHST- 2021/06/21 00:00 [accepted]
PHST- 2021/07/26 06:37 [entrez]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/07/27 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.709877 [doi]
PST - epublish
SO  - Front Oncol. 2021 Jul 9;11:709877. doi: 10.3389/fonc.2021.709877. eCollection 
      2021.