The potential value of immunotherapy in colorectal cancers : review of the evidence for programmed death-1 (PD-1) inhibitor therapy

BACKGROUND: Colorectal cancers have been identified as potential targets for immunotherapy with programmed cell death-1 (PD-1) inhibitors. METHOD: English-language publications from MEDLINE and Embase evaluating PD-1/PD-L1 in the CRC tumour microenvironment and clinical trials assessing PD-1 inhibitors were included. Sixteen abstracts were screened. Fifteen met the inclusion criteria. After review of the full texts, this resulted in a final reference list of eight studies eligible for review. RESULTS: Five studies assessing PD-1/PD-L1 in CRC and three trials assessing PD-1 inhibitors were included. PD-1+ tumour infiltrating lymphocytes (TILs) and PD-L1+ cancer cells featured more prominently in MSI-H CRCs when compared with MSS CRCs, except in one study where PD-L1 expression was higher in MSS CRCs. In the three trials assessing PD-1 inhibitor, all three studies recruited metastatic CRC (mCRC) patients. One study also included recurrent CRC (rCRC). The objective response as per the Response Evaluation Criteria in Solid Tumours (RECIST) criteria was 0% (19 colorectal cancer patients, MSI status unknown) in the nivolumab study. In the pembrolizumab study, objective response to PD-1 inhibitor was 40% and 0% in MSI-H and MSS mCRCs respectively (10 patients in MSI-H group, 18 patients in MSS group). 78% of patients in the MSI-H mCRC group compared to 11% in the MSS mCRC group (p