Non-invasive test to predict response to therapy in colorectal cancer patients

Abstract

The invention is a method of predicting response to therapy in a colorectal cancer patient, the method comprising analysis of circulating tumor DNA from a patient's sample.

1 . A method for identifying a colorectal cancer patient in stage II, III, or IV as likely to positively respond to an anti-tumor therapy regimen with increased progression-free survival (PFS), wherein the method comprises the steps of:
 (a) providing a cell-free blood sample obtained from the patient;   (b) determining the sequence of at least a portion of each of the biomarkers listed in Table 1;   (c) measuring the frequency of mutant alleles; and   (d)(i) identifying the patient as likely to positively respond to a therapy regimen if the frequency of mutant alleles is below a median documented for colorectal cancer patients at the same stage; or   (d)(ii) identifying the patient as not likely to positively respond to a therapy regimen if the frequency of mutant alleles is above a median documented for colorectal cancer patients at the same stage.   
     
     
         2 . The method of  claim 1 , wherein the sequences of at least a portion of all of the biomarkers listed in Table 1 are determined. 
     
     
         3 . The method of  claim 1 , wherein the therapy regimen is selected from treatment with FOLFOXIRI-bevacizumab and treatment with FOLFOX-bevacizumab. 
     
     
         4 . The method of  claim 3 , wherein the treatment with FOLFOXIRI-bevacizumab is selected from concurrent and sequential. 
     
     
         5 . The method of  claim 1 , further comprising a step of administering the therapy if the patient is identified as likely to positively respond to the therapy regimen. 
     
     
         6 - 8 . (canceled) 
     
     
         9 . A method of treatment of a colorectal cancer patient in stage II, III, or IV, wherein the method comprises the steps of:
 (a) providing a cell-free blood sample obtained from the patient;   (b) determining the sequence of at least a portion of each of the biomarkers listed in Table 1;   (c) measuring the frequency of mutant alleles; and   (d)(i) identifying the patient as likely to positively respond to an anti-tumor therapy regimen if the frequency of mutant alleles is below a median documented for colorectal cancer patients at the same stage; or   (d)(ii) identifying the patient as not likely to positively respond to an anti-tumor therapy regimen if the frequency of mutant alleles is above a median documented for colorectal cancer patients at the same stage; and   (e) administering the therapy regimen to the patient identified as likely to positively respond to the therapy regimen.   
     
     
         10 . A method of  claim 9 , wherein at least a partial sequence of all the biomarkers listed in Table 1 are determined. 
     
     
         11 . The method of  claim 9 , wherein the therapy regimen is selected from concurrent and sequential FOLFOXIRI-bevacizumab. 
     
     
         12 . (canceled)