Immunotherapeutic agents approved for the treatment of colorectal cancer include monoclonal antibodies that target the epidermal growth factor receptor (EGFR) and VEGF.
Approved immunotherapeutic agents
Combination therapy/treatment algorithms
Approved immunotherapeutic agents (for colorectal cancer)
In 2004, the EGFR inhibitor cetuximab (Erbitux, Eli Lilly) and the VEGF inhibitor bevacizumab (Avastin, Genentech) were approved for the treatment of metastatic colorectal carcinoma.
- Cetuximab is a monoclonal antibody that inhibits EGFR activity; EGFR is overexpressed in some colorectal cancers.
- The monoclonal antibody bevacizumab inhibits the activity of VEGF, a protein that promotes tumor growth by increasing vascularization (Figure 1).
Figure 1. Bevacizumab mechanism of action.
A second EGFR inhibitor, panitumumab (Vectibix, Amgen), was approved in 2006 for the treatment of colorectal cancer that has metastasized despite systemic chemotherapy. Panitumumab was the first fully human monoclonal antibody to receive FDA approval for the treatment of cancer.
Ramucirumab (Cyramza, Eli Lilly), a monoclonal antibody directed against the VEGF receptor 2 (VEGFR-2), was approved in 2015 for second-line therapy in combination with the chemotherapy regimen FOLFIRI for the treatment of metastatic colorectal cancer.
Colorectal cancer combination therapy/treatment algorithms
The NCI makes the following recommendations for the first-line treatment of advanced or metastatic colorectal cancer:
- FOLFOX with bevacizumab;
- FOLFIRI with bevacizumab;
- FOLFOXIRI with bevacizumab; or
- FOLFIRI with cetuximab.
For patients who have disease progression following the above treatment regimens, the NCI recommends:
- Cetuximab with or without irinotecan for patients who have progressed on irinotecan-containing chemotherapy regimens;
- FOLFIRI and ramucirumab for patients who have progressed following treatment with FOLFOX and bevacizumab; or
- Panitumumab alone or with chemotherapy in patients who have progressed following chemotherapy.
Current clinical trials for colorectal cancer
Several immunotherapeutic agents that have already been approved for the treatment of other solid tumors are under investigation for the treatment of colorectal cancer, including the PD-1/PD-L1 checkpoint inhibitors pembrolizumab, nivolumab (with or without ipilimumab), durvalumab and atezolizumab. Investigative agents such as the CTLA-4 inhibitor tremelimumab (AstraZeneca) and the anti-CD27 monoclonal antibody varlilumab are also in clinical trials for the treatment of colorectal cancer.
An immune-modulating vaccine called Imprime PGG (Biothera) is currently in phase 3 testing for the treatment of recurrent or progressive colorectal cancer in patients without a KRAS mutation (called KRAS wild-type). The vaccine activates the innate immune response, boosting the efficacy of monoclonal antibodies such as cetuximab and pembrolizumab.
Other immunotherapies are in phase 1/2 clinical trials, including dendritic cell and peptide vaccines, chimeric antigen receptor (CAR) T-cell therapy and oncolytic viruses.