Multicenter randomized phase 2 trial of neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer

In single-arm studies of locally advanced rectal cancer (LARC), the combination of radiotherapy with immune checkpoint inhibitors resulted in high pathological complete response (pCR) rates. A randomized phase 2 trial at 8 centers in Beijing (China) evaluated neoadjuvant chemoradiation (CRT) with or without PD-1 blockade for LARC. A total of 186 patients were randomized to neoadjuvant CRT with concurrent PD-1 blockade (experimental group A), neoadjuvant CRT with sequential PD-1 blockade (experimental group B) or neoadjuvant CRT alone (control group). Radical surgeries were scheduled after neoadjuvant treatments. The primary endpoint was pCR rate. The pCR rates were 27.1%, 32.7%, and 14.0% for experimental groups A and B and the control group, respectively. The difference between experimental group B and the control group reached statistical significance (risk ratio 2.332; p=0.019). No substantial difference between the groups were seen regarding adverse reactions, surgical complications, or disease progression. The authors conclude that adding PD-1 blockade after neoadjuvant CRT increased the pCR rate for patients with LARC and raises no substantial safety concerns.