Abstract 3440
Background
RAS testing is used to select patients sensitive to anti-EGFR therapies in metastatic colorectal cancer (mCRC) but other biomarkers such as BRAF, PIK3CA/PTEN and p-IGF-1R+/MMP7 + (DP phenotype) have not prospectively assessed to predict anti-EGFR resistance.
Methods
We designed a multicenter prospective trial (NCT01276379) to evaluate if the following biomarkers BRAF mutation, PIK3CA mutation/PTEN loss and DP phenotype can improve the prediction of 12-months progression-free survival (PFS) over the use of only clinical variables in patients with RAS WT mCRC treated with standard chemotherapy plus biweekly Cetuximab as first-line therapy. The planned sample size was 170 RAS WT patients to detect a 20% difference in 12-month PFR based on analysis of clinical and selected biomarkers (alpha=.05, beta=.2). The discriminatory capacity of the biomarkers was evaluated using ROC curves.
Results
We included 181 RAS WT patients. The biomarker distribution was: BRAF mutant 20 patients (11%), PIK3CA mutated/PTEN loss 98 patients (58%) and DP 23 patients (12.7%). Median PFS: BRAF WT 11.4 vs BRAF mutant 5.9 months (p = 0.004). PIK3CA/PTEN pathway and DP phenotype did not discriminate PFR (p=NS). Baseline clinical variables with good prognosis in a multivariable model were PS = 0, left sided tumor and resectable liver metastases (i.e. liver only metastases (<3 nodules and <5cm)).
Conclusions
A clinical score discriminates between two groups of patients who benefitted differently from chemotherapy plus cetuximab. The addition of BRAF, PIK3CA/PTEN and DP to the clinical score does not improve the prediction of 12m PFS.
Clinical trial identification
EudraCT: 2010-019236-12.
Legal entity responsible for the study
Grupo Español Multidisciplinar de Cáncer Digestivo.
Funding
Merck.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.