HER2 Status in Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma for Entry to the TRIO-013/LOGiC Trial of Lapatinib.
HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1%) had HER2-amplified disease with 29 (1.5%) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3%; GEJ, 8.3% and esophageal cancer, 4.4%), 487 patients (89%) were centrally confirmed as having HER2-amplified disease. Concordance between central and local HER2 testing was 83%. Concordance between PathVysion and IQ PharmDx FISH assays was 99% and FISH in the two central laboratories was 95%. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression-free survival (PFS), particularly among those whose cancers had 5.01-10.0 and >10.0-fold amplification of HER2 In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low. Mol Cancer Ther; 16(1); 228-38. ©2016 AACR.
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California. press@usc.edu.
Michael F
MF
Press
GlaxoSmithKline, Philadelphia, Pennsylvania.
Catherine E
CE
Ellis
Bristol-Myers Squibb Company, Princeton, New Jersey.
Robert C
RC
Gagnon
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Tobias J
TJ
Grob
International Drug Development Institute, Leuven, Belgium.
Marc
M
Buyse
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Ivonne
I
Villalobos
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, P.R. China.
Zhiyong
Z
Liang
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, P.R. China.
Shafei
S
Wu
Seoul National University College of Medicine, Seoul, Republic of Korea.
Yung-Jue
YJ
Bang
PLA Cancer Center, Nanjing Bayi Hospital, Jiangsu, China.
Shu-Kui
SK
Qin
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Hyun Cheol
HC
Chung
The Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China.
Jianming
J
Xu
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Joon Oh
JO
Park
Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
Krzysztof
K
Jeziorski
Translational Research in Oncology, Paris, France.
Karen
K
Afenjar
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Yanling
Y
Ma
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Monica C
MC
Estrada
Novartis Pharmaceutical Corporation, East Hanover, New Jersey.
Douglas M
DM
Robinson
Novartis Pharmaceutical Corporation, East Hanover, New Jersey.
Stefan J
SJ
Scherer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Guido
G
Sauter
Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, California.
J Randolph
JR
Hecht
Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, California.
Dennis J
DJ
Slamon
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human