Plasma arginine as predictive biomarker for outcomes with immune checkpoint inhibition for metastatic colorectal cancer

The Canadian CO.26 trial randomized patients with refractory metastatic colorectal cancer (mCRC) to durvalumab plus tremelimumab (D+T) or best supportive care (BSC). Post hoc analysis of CO.26 compared outcomes in patients with baseline plasma arginine above versus below the median level of 10,700 ng/ml. In the BSC arm, the baseline plasma arginine level was not significantly associated with overall survival, whereas in the D+T arm high baseline plasma arginine was associated with significantly improved overall survival. In the arginine-high group, D+T significantly improved overall survival versus BSC, whereas this was not the case in the arginine-low group. The authors conclude that high baseline plasma arginine was predictive of improved overall survival in patients receiving D+T for mCRC. Therapeutic approaches targeting the arginine pathway may augment activity of immune checkpoint inhibition.