Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Sartore-Bianchi
Andrea
A
Divisione Oncologia Falck, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. salvatore.siena@ospedaleniguarda.it
Moroni
Mauro
M
Veronese
Silvio
S
Carnaghi
Carlo
C
Bajetta
Emilio
E
Luppi
Gabriele
G
Sobrero
Alberto
A
Barone
Carlo
C
Cascinu
Stefano
S
Colucci
Giuseppe
G
Cortesi
Enrico
E
Nichelatti
Michele
M
Gambacorta
Marcello
M
Siena
Salvatore
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D012372:ROC Curve; D015996:Survival Rate; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab