HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients

V. Martin, L. Landi, F. Molinari, G. Fountzilas, R. Geva, A. Riva, P. Saletti, S. De Dosso, A. Spitale, S. Tejpar, K. T. Kalogeras, L. Mazzucchelli, M. Frattini*, F. Cappuzzo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Background: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease. Methods: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab. Results: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17≥2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH-profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively). Conclusion: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.

Original languageEnglish
Pages (from-to)668-675
Number of pages8
JournalBritish Journal of Cancer
Volume108
Issue number3
DOIs
StatePublished - 19 Feb 2013
Externally publishedYes

Funding

FundersFunder number
Associazione Oncologia Traslazionale
Belgian Federation Against Cancer
Belgian National Cancer Plan
Fondazione Ticinese contro il Cancro
Associazione Italiana per la Ricerca sul Cancro

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