Checkpoint Inhibitors for the Treatment of Advanced Colorectal Cancer

One of the most interesting abstracts at the recent 2015 ASCO meeting was a presentation by Dr. Le from Johns Hopkins. This work, which was presented at ASCO and printed online in the NEJM "PD-1 Blockade in Tumors with Mismatch-Repair Deficiency," in my view was one of the most compelling papers of the meeting.

Pembrolizumab 10 mg/kg was administered every 2 weeks in patients with metastatic colon cancer with or without mismatch repair deficiency.

CONCLUSIONS and MY COMMENTS:

1) Whole genome sequencing demonstrated 1782 somatic mutations per tumor in mismatch repair deficient tumors compared to 73 mutations in mismatch repair proficient tumors

2) Checkpoint inhibition of PD-1 is more effective when more somatic mutations are present

3) Increased number of somatic mutations create a target rich environment for activated T cells

4) The creation of neoepitopes results in more favorable response with checkpoint inhibition

5) Objective response rates for colorectal cancer mismatch proficient tumors was 0%

6) Objective response rate for mismatch repair deficient colorectal tumors PFS of 40% and immune related PFS of 78%

7) This remarkable paper is noteworthy for targeting EXPENSIVE yet EFFECTIVE therapy to the right group of patients

8) This paper also extended, in preliminary fashion, the same molecular targeting concept to tumors other than colorectal cancer

For more information, please contact Dr. Steven Mamus. 

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03 June 2015, 14:53
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