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 |
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| 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 |
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| Institution: | 1. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; 2. Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; 3. Unit of Medical Statistics Biometry& Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; University General Hospital of Heraklion and Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece, |
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| Abstract: | IntroductionAlthough 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 MethodsWe 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.ResultsNo 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).ConclusionGain 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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