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.
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 / F. Pietrantonio, C. Maggi, M. Di Bartolomeo, M.G. Facciorusso, F. Perrone, A. Testi, R. Iacovelli, R. Miceli, I. Bossi, G. Leone, M. Milione, G. Pelosi, F. De Braud. - In: PLOS ONE. - ISSN 1932-6203. - 9:4(2014 Apr), pp. e92147.1-e92147.6.
|Titolo:||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|
PIETRANTONIO, FILIPPO (Primo)
MAGGI, CLAUDIA (Secondo)
PELOSI, GIUSEPPE (Penultimo)
DE BRAUD, FILIPPO GUGLIELMO MARIA (Ultimo)
|Parole Chiave:||adult; aged; aged, 80 and over; colorectal neoplasms; demography; disease-free survival; female; GTP phosphohydrolases; humans; in situ hybridization, fluorescence; male; membrane proteins; middle aged; nuclear proteins; proto-oncogene proteins B-raf; receptor protein-tyrosine kinases; receptor, epidermal growth factor; transcription factors; treatment outcome; gene dosage; agricultural and biological sciences (all); biochemistry, genetics and molecular biology (all); medicine (all)|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||apr-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0092147|
|Appare nelle tipologie:||01 - Articolo su periodico|