TY - JOUR
T1 - Gain of ALK gene copy number may predict lack of benefit from anti-EGFR treatment in patients with advanced colorectal cancer and RAS-RAF-PI3KCA wild-type status
AU - Pietrantonio, Filippo
AU - Maggi, Claudia
AU - Di Bartolomeo, Maria
AU - Facciorusso, Maria Grazia
AU - Perrone, Federica
AU - Testi, Adele
AU - Iacovelli, Roberto
AU - Miceli, Rosalba
AU - Bossi, Ilaria
AU - Leone, Giorgia
AU - Milione, Massimo
AU - Pelosi, Giuseppe
AU - De Braud, Filippo
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Introduction: Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations. Patients and Methods: We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number - defined as mean of 3 to 5 fusion signals in ≥10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease. Results: No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885). Conclusion: Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.
AB - Introduction: Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations. Patients and Methods: We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number - defined as mean of 3 to 5 fusion signals in ≥10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease. Results: No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885). Conclusion: Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.
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U2 - 10.1371/journal.pone.0092147
DO - 10.1371/journal.pone.0092147
M3 - Article
C2 - 24691006
AN - SCOPUS:84898875151
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e92147
ER -