Immune checkpoint blockade (ICB) has revolutionized treatment for many cancer types, including advanced metastatic cancer. Following these successes, clinical evaluation has expanded to earlier disease settings, including surgically resectable disease. The possible advantages of this neoadjuvant therapy include shrinkage of the tumor before therapy, the eradication of micrometastases and the generation of a potent T cell response earlier in the disease course. Nevertheless, adverse events and toxicity need to be carefully evaluated and weighed against the possible clinical benefits. On the basis of these concepts, a large number of trials are underway to test the value of neoadjuvant ICB in single-arm trials or to directly compare neoadjuvant settings versus adjuvant settings in larger randomized studies across different cancer types. Three such studies published in the New England Journal of Medicine this year present impressive results.

First, Chalabi et al. demonstrated the value of neoadjuvant ICB in the single-arm NICHE-2 phase 2 trial. The investigators administered neoadjuvant nivolumab plus ipilimumab to 111 patients with non-metastatic, locally advanced and previously untreated mismatch-repair-deficient colon cancer. The authors reported that none of the patients had to discontinue treatment because of adverse events, and they observed a pathological response in 109 of 111 patients. An impressive 95% (105) of the patients showed a major pathological response, and at a median follow-up of 26 months, none of the patients had signs of disease recurrence.