Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604).
Eur J Cancer
; 105: 41-49, 2018 12.
Article
in En
| MEDLINE
| ID: mdl-30391779
ABSTRACT
BACKGROUND:
Anti-HER2 therapy has not demonstrated a survival advantage in the second-line setting of patients with HER2-positive gastric cancer. We conducted this study to assess changes in HER2 status and to identify possible biomarkers for acquired resistance after the use of trastuzumab as the first-line therapy. PATIENTS ANDMETHODS:
Patients with advanced or recurrent HER2-positive gastric adenocarcinoma who were diagnosed with progressive disease after the first-line trastuzumab-based therapy and developed pathologically confirmed adenocarcinoma within 3 months after completion of trastuzumab-based therapy were enrolled in this study. We collected re-biopsied samples from the HER2-positive patients who had developed resistance to trastuzumab and re-evaluated their HER2 status. Amplification of EGFR and c-met, as well as PIK3CA mutation, were comparatively analysed when samples were available.RESULTS:
Among 33 eligible patients, loss of HER2 was identified in 20 patients (60.6%) with refractory disease. Immunohistochemistry showed that the rate of HER2 overexpression was greatly reduced after therapy (pre-HER2 3+ 24 [72.7%] vs. post-HER2 3+ 13 [39.4%]). We found that the use of fixatives other than 10% neutral buffered formalin significantly reduced the HER2-positive rate. EGFR amplification, c-met amplification and PIK3CA mutation before and after trastuzumab-based therapy were observed in 10.3% and 3.8%, 17.9% and 4.2% and 4.0% and 4.2% of cases, respectively.CONCLUSION:
Re-evaluation of HER2 status is needed to determine the appropriate use of anti-HER2-targeted therapy after disease progression. Our results also highlight the importance of formalin fixation conditions for HER2 testing.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Adenocarcinoma
/
Receptor, ErbB-2
/
Genes, erbB-2
/
Drug Resistance, Neoplasm
/
Trastuzumab
/
Antineoplastic Agents, Immunological
/
Neoplasm Proteins
Type of study:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
Language:
En
Journal:
Eur J Cancer
Year:
2018
Document type:
Article
Affiliation country:
Japan