PMID- 25514804
OWN - NLM
STAT- MEDLINE
DCOM- 20151208
LR  - 20181202
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 10
IP  - 4
DP  - 2015 Apr
TI  - Phase II study of afatinib, an irreversible ErbB family blocker, in EGFR 
      FISH-positive non-small-cell lung cancer.
PG  - 665-72
LID - 10.1097/JTO.0000000000000442 [doi]
AB  - INTRODUCTION: Afatinib, an oral irreversible ErbB Family Blocker, has 
      demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) 
      mutation-positive advanced lung adenocarcinoma. It is unknown whether such 
      activity also occurs in patients with EGFR gene overexpression, regardless of 
      mutation status. This phase II study investigated the activity and safety of 
      afatinib in advanced non-small-cell lung cancer with increased EGFR gene copy 
      number and/or gene amplification by fluorescence in situ hybridization (FISH), 
      with or without EGFR mutation. METHODS: EGFR gene overexpression was assessed by 
      FISH analysis; patients with high polysomy or gene amplification were considered 
      FISH positive. Patients received daily afatinib less than or equal to 50 mg 
      (monotherapy). Endpoints included objective response rate (ORR; primary), disease 
      control rate (DCR), progression-free survival (PFS), overall survival (OS), and 
      safety. RESULTS: Of 223 patients screened, 69 patients were FISH-positive and met 
      eligibility criteria for treatment. The ORR was 13.0% overall (n =9 of 69). 
      Higher ORRs were observed in patients with gene amplification (20.0%; n =5 of 25) 
      and EGFR mutation-positive tumors (25.0%; n =3 of 12). The DCR was 50.7% overall 
      (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients 
      with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR 
      mutation-positive tumors 66.7% (n = 8 of 12). In the overall population, median 
      PFS was 8.4 weeks and median OS was 50.4 weeks. The most common afatinib-related 
      adverse events were rash/acne (83%) and diarrhea (78%). CONCLUSIONS: First- or 
      second-line afatinib demonstrated preliminary activity and manageable safety in 
      EGFR FISH-positive patients with advanced non-small-cell lung cancer.
FAU - Cappuzzo, Federico
AU  - Cappuzzo F
AD  - *Istituto Toscano Tumori, Ospedale Civile di Livorno, Livorno, Italy; daggerHumanitas 
      Cancer Center, Istituto Clinico Humanitas IRCCS, Rozzano, Italy; double daggerIRCCS AOU San 
      Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Lung Cancer Unit, 
      Genova, Italy;  section signSan Gerardo Hospital, Monza, Italy;  ||Istituto Oncologico Veneto 
      IRCSS, Padova, Italy;  paragraph signClinical Research Center, Center of Excellence on Aging, 
      University Foundation, Chieti, Italy; #IRCCS Humanitas Clinical Institute, 
      Rozzano, Milan, Italy; **Boehringer Ingelheim Pharma GmbH & Co. KG, Vienna, 
      Austria; daggerdaggerBoehringer Ingelheim Italia SpA, Milan, Italy; and double daggerdouble daggerBoehringer 
      Ingelheim Ltd., Bracknell, UK.
FAU - Finocchiaro, Giovanna
AU  - Finocchiaro G
FAU - Grossi, Francesco
AU  - Grossi F
FAU - Bidoli, Paolo
AU  - Bidoli P
FAU - Favaretto, Adolfo
AU  - Favaretto A
FAU - Marchetti, Antonio
AU  - Marchetti A
FAU - Valente, Maria Luisa
AU  - Valente ML
FAU - Cseh, Agnieszka
AU  - Cseh A
FAU - Clementi, Laura
AU  - Clementi L
FAU - Massey, Dan
AU  - Massey D
FAU - Santoro, Armando
AU  - Santoro A
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
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 (DNA, Neoplasm)
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Afatinib
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology
MH  - DNA, Neoplasm/*analysis
MH  - ErbB Receptors/*genetics/metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Genes, erbB-1/*drug effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Lung Neoplasms/*drug therapy/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Quinazolines/*therapeutic use
EDAT- 2014/12/17 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/17 06:00
PHST- 2014/12/17 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S1556-0864(15)32369-8 [pii]
AID - 10.1097/JTO.0000000000000442 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2015 Apr;10(4):665-72. doi: 10.1097/JTO.0000000000000442.