Immune therapy for advanced colorectal cancer (mCRC)
Immune checkpoint inhibitors show promising results in the treatment of rare mCRC cases with high microsatellite instability.
Colorectal cancer is one of the most common cancer diagnoses worldwide and one of the leading causes of cancer related mortality. Alltough the biology is well understood, the prognosis for metastasised colorectal cancer (mCRC) is still poor. This is specially the case in patients with high microsatellite instability, an impairment of DNA mismatch repair that leads to an accumulation of errors and indicates a high mutational load.
Combined therapies
Alone or in combination with other treatment types such as chemotherapy and/or radiation therapy immune checkpoint inhibitors such as nivolumab have revolutionised the treatment of different tumor types. In cases of NSCLC, Hodgkin’s lymphoma, melanoma and renal cell carcinoma PD-1/PD-L1 inhibition has become part of the treatment algorithm. The combination with ipilimumab was found to be promising, a randomised study however is needed.
Nivolumab as first line treatment?
Phase II trials have suggested that patients with highly mutated tumors benefit from immune checkpoint inhibition. Recent results from the CheckMate 142 trial show that patients who underwent two prior chemotherpies instead of three showed the most robust results. The data suggests considering nivolumab as a first line treatment in mCRC patients.
Biomarkers
In absence of a solid, reproducible method to determine the status of DNA missmatch repair (MMR protein expression), other predictive markers were evaluated. KRAS and BRAF mutations are potential predictors of response to anti-PD-1 therapy. Overexpression of PD-L1 however did not appear to predict treatment response.
Reference
Sarshekeh, Overman and Kopetz Nivolumab in the treatment of microsatellite instability high metastatic colorectal cancer. Future Oncol. 10.2217/fon-2017-0696 (ahead of print)