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.

Abstract

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.

• Authors: Filippo Pietrantonio, Claudia Maggi, Maria Di Bartolomeo, Maria Grazia Facciorusso, Federica Perrone, Adele Testi, Roberto Iacovelli, Rosalba Miceli, Ilaria Bossi, Giorgia Leone, Massimo Milione, Giuseppe Pelosi, Filippo de Braud
• Journal: PloS one (PLoS One) Vol. 9 Issue 4 Pg. e92147 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24691006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Nuclear Proteins
• PI3KCA protein, human
• Transcription Factors
• ALK protein, human
• Anaplastic Lymphoma Kinase
• ErbB Receptors
• Receptor Protein-Tyrosine Kinases
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• GTP Phosphohydrolases
• NRAS protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Anaplastic Lymphoma Kinase
• Colorectal Neoplasms (drug therapy)
• Demography
• Disease-Free Survival
• ErbB Receptors (antagonists & inhibitors, metabolism)
• Female
• GTP Phosphohydrolases (genetics)
• Gene Dosage
• Humans
• In Situ Hybridization, Fluorescence
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Nuclear Proteins (genetics)
• Proto-Oncogene Proteins B-raf (genetics)
• Receptor Protein-Tyrosine Kinases (genetics)
• Transcription Factors (genetics)
• Treatment Outcome