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Epidermal Growth Factor Receptor Gene Copy Number and Clinical Outcome of Metastatic Colorectal Cancer Treated With Panitumumab

Andrea Sartore-Bianchi, Mauro Moroni, Silvio Veronese, Carlo Carnaghi, Emilio Bajetta, Gabriele Luppi, Alberto Sobrero, Carlo Barone, Stefano Cascinu, Giuseppe Colucci, Enrico Cortesi, Michele Nichelatti, Marcello Gambacorta, Salvatore Siena

From the Ospedale Niguarda Ca' Granda; Istituto Nazionale Tumori, Milan; Istituto Clinico Humanitas, Rozzano; Università Modena e Reggio Emilia, Modena; Ospedale San Martino, Genova; Policlinico Gemelli, Università Cattolica; Policlinico Umberto I, Università La Sapienza, Rome; Università Politecnica Marche, Ancona; and Istituto Tumori Giovanni Paolo II, Bari, Italy

Address reprint requests to Salvatore Siena, MD, Divisione Oncologia Falck, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy; e-mail: salvatore.siena{at}ospedaleniguarda.it

Purpose In a previous cohort study, we proposed that responsiveness of metastatic colorectal cancer (mCRC) to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies has a genetic basis, being associated with increased EGFR gene copy number (GCN) as measured by fluorescence in situ hybridization (FISH) in individual tumors. The present study was aimed at assessing the predictive role of EGFR GCN, in terms of clinical outcome, in patients treated with panitumumab.

Patients and Methods Patients with mCRC refractory to standard therapies were a subset of patients from a phase III trial of panitumumab plus best supportive care (BSC; n = 58) versus BSC alone (n = 34) who were selected on the basis of availability of tumor samples adequate for FISH.

Results In patients treated with panitumumab, a mean EGFR GCN of less than 2.5/nucleus or less than 40% of tumor cells displaying chromosome 7 polysomy within the tumor predicted for shorter progression-free survival (PFS; P = .039 and P = .029, respectively) and overall survival (P = .015 and P = .014, respectively). None of the treated patients with mean EGFR GCN of less than 2.47/nucleus or less than 43% of tumor cells displaying chromosome 7 polysomy obtained objective response compared with six of 20 and six of 19 patients with values greater than these cutoff limits, respectively (P = .0009 and P = .0007, respectively). Evaluation of BSC-treated patients showed no correlation between EGFR GCN or chromosome 7 polysomy status and PFS.

Conclusion In a larger and more homogeneous series than in previous studies, present exploratory data suggest that mCRC patients with tumors distinguishable by FISH analysis of EGFR as homogenously disomic or with low chromosome 7 polysomy have a reduced likelihood of response to panitumumab.

Supported by research grants from Associazione Italiana Ricerca Cancro and Oncologia Ca' Granda ONLUS Fondazione.

A.S.-B., M.M., and S.V. contributed equally to this work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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