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PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer
Journal of Clinical Oncology, 06/01/09

Loupakis F et al. - PTEN loss in metastases may be predictive of resistance to cetuximab plus irinotecan. The combination of PTEN IHC and KRAS mutational analyses could help to identify a subgroup of pts with metastatic colorectal cancer (mCRC) who have higher chances of benefiting from EGFR inhibition.

Methods

A retrospective study to investigate:
- the role of PTEN loss
- AKT phosphorylation, and
- KRAS mutations
  on the activity of cetuximab plus irinotecan in pts with mCRC
Pts with irinotecan-refractory mCRC who were treated with cetuximab plus irinotecan was tested for PTEN and pAKT IHC, and KRAS mutations
Analyses were performed both on primary tumors and on related metastases
Association among IHC, mutational results, and treatment outcomes was investigated

Results

102 pts were eligible; 96 primary tumors, 59 metastases, and 53 paired samples were available
58% of assessable samples were PTEN-positive; 40% were pAKT-positive
Levels of concordance between primary tumors and metastases were 60%, 68%, and 95% for PTEN, pAKT, and KRAS, respectively
PTEN status on primary tumors and pAKT status both on primary tumors and on metastases did not predict response or PFS
On metastases, 36% of pts with PTEN-positive tumors were responders vs 5% who had PTEN-negative tumors
Median PFS of pts with PTEN-positive metastases was 4.7 mo vs 3.3 mo for those with PTEN-negative metastases
Pts with PTEN-positive metastases and KRAS wild type had longer PFS vs other pts

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