PMID- 30105460
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20190729
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 82
IP  - 4
DP  - 2018 Oct
TI  - Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer 
      according to HER2neu and EGFR status: a randomized placebo-controlled phase II 
      study (EORTC 40071).
PG  - 733-739
LID - 10.1007/s00280-018-3667-8 [doi]
AB  - PURPOSE: HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall 
      survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits 
      both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with 
      epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS: Tumors 
      from chemotherapy-naive patients were screened centrally by fluorescence in situ 
      hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or 
      HER2neu expression or amplification were allocated to three strata based on 
      EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), 
      with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was 
      progression-free survival (PFS) in stratum 3. RESULTS: 29 of 72 screened patients 
      were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu-: by 
      FISH/+ by IHC, n = 5) and 3 (HER2neu-/EGFR+, n = 18), of which 28 patients were 
      eligible (14 per arm). Enrollment was curtailed after announcement of the 
      negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 
      95% CI 0.37-1.99) in the per protocol population, and 8.0 versus 6.3 months 
      (HR = 0.85, 95% CI 0.30-2.46) for stratum 3, in the lapatinib versus placebo arm 
      respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% 
      CI 0.35-2.27). There were no safety concerns. CONCLUSIONS: Central EGFR and 
      HER2neu stratification by IHC and FISH can be used for further pan-HER 
      strategies. Lapatinib with ECF/X was well tolerated, but did not show clear 
      activity in patients with metastatic GC.
FAU - Moehler, Markus
AU  - Moehler M
AD  - I. Department of Internal Medicine, Johannes Gutenberg University of Mainz, 
      Mainz, Germany. markus.moehler@unimedizin-mainz.de.
AD  - I. Department of Internal Medicine, University Medical Center Mainz, 
      Langenbeckstr. 1, 55131, Mainz, Germany. markus.moehler@unimedizin-mainz.de.
FAU - Schad, Arno
AU  - Schad A
AD  - Institute of Pathology, Johannes Gutenberg University of Mainz, Mainz, Germany.
FAU - Maderer, Annett
AU  - Maderer A
AD  - I. Department of Internal Medicine, Johannes Gutenberg University of Mainz, 
      Mainz, Germany.
FAU - Atasoy, Ajlan
AU  - Atasoy A
AD  - EORTC Headquarters, Brussels, Belgium.
FAU - Mauer, Murielle E
AU  - Mauer ME
AD  - EORTC Headquarters, Brussels, Belgium.
FAU - Caballero, Carmela
AU  - Caballero C
AD  - EORTC Headquarters, Brussels, Belgium.
FAU - Thomaidis, Thomas
AU  - Thomaidis T
AD  - I. Department of Internal Medicine, Johannes Gutenberg University of Mainz, 
      Mainz, Germany.
FAU - John, Jestinah M Mahachie
AU  - John JMM
AD  - EORTC Headquarters, Brussels, Belgium.
FAU - Lang, Istvan
AU  - Lang I
AD  - National Institute of Oncology, Budapest, Hungary.
FAU - Van Cutsem, Eric
AU  - Van Cutsem E
AD  - University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium.
FAU - Freire, Joao
AU  - Freire J
AD  - Instituto Portugues de Oncologia Francisco Gentil, Lisbon, Portugal.
FAU - Lutz, Manfred P
AU  - Lutz MP
AD  - Department of Internal Medicine, Caritasklinikum St. Theresia, Saarbrucken, 
      Germany.
FAU - Roth, Arnaud
AU  - Roth A
AD  - Department of Oncosurgery, University of Geneva, Geneva, Switzerland.
CN  - EORTC Gastrointestinal Tract Cancer Group
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
DEP - 20180813
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0VUA21238F (Lapatinib)
RN  - 3Z8479ZZ5X (Epirubicin)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U3P01618RT (Fluorouracil)
RN  - FPEPIR regimen
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects
MH  - Cisplatin/administration & dosage/adverse effects
MH  - Epirubicin/administration & dosage/adverse effects
MH  - ErbB Receptors/antagonists & inhibitors/metabolism
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - *Lapatinib/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Progression-Free Survival
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects
MH  - *Receptor, ErbB-2/antagonists & inhibitors/metabolism
MH  - *Stomach Neoplasms/drug therapy/pathology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Advanced gastric cancer
OT  - EGFR
OT  - First-line
OT  - HER2neu
OT  - Lapatinib
OT  - Placebo-controlled
EDAT- 2018/08/15 06:00
MHDA- 2019/07/30 06:00
CRDT- 2018/08/15 06:00
PHST- 2018/04/07 00:00 [received]
PHST- 2018/08/09 00:00 [accepted]
PHST- 2018/08/15 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/08/15 06:00 [entrez]
AID - 10.1007/s00280-018-3667-8 [pii]
AID - 10.1007/s00280-018-3667-8 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2018 Oct;82(4):733-739. doi: 
      10.1007/s00280-018-3667-8. Epub 2018 Aug 13.