| Title: |
Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial |
| Authors: |
Yang, Yingchi, Pang, Kai, Lin, Guole, Liu, Xinzhi, Gao, Jiale, Zhou, Jiaolin, Xu, Lai, Gao, Zhidong, Wu, Yingchao, Li, Ang, Han, Jiagang, Wu, Guoju, Wang, Xin, Li, Fei, Ye, Yingjiang, Zhang, Jie, Chen, Guangyong, Wang, Hao, Kong, Yuanyuan, Wu, Aiwen, Xiao, Yi, Yao, Hongwei, Zhang, Zhongtao |
| Source: |
Nature Medicine; 20250101, Issue: Preprints p1-8, 8p |
| Abstract: |
Radiotherapy displays unique antitumor synergism with immune checkpoint inhibitors, which is indicated by high pathological complete response (pCR) rates from single-arm trials of locally advanced rectal cancer (LARC). Here we test the efficacy and safety of the radiation–immune checkpoint inhibitor combination in patients with LARC in a phase 2, randomized trial conducted in eight major colorectal cancer centers in Beijing. In total, 186 eligible all-comer (proficient mismatch repair and deficient mismatch repair) participants were enrolled. The patients were randomly assigned to receive neoadjuvant chemoradiation + concurrent/sequential PD-1 blockade (experiment groups A/B) or neoadjuvant chemoradiation alone (control group). Radical surgeries were scheduled after neoadjuvant treatments. The primary endpoint was the pCR rate. The pCR rates were 27.1%, 32.7% and 14.0% for experiment groups A and B and the control group, respectively. The difference in pCR rates between experiment group B and the control group reached statistical significance (risk ratio 2.332, 95% confidence interval 1.106–4.916; P= 0.019). No substantial differences between either one of the experiment groups and the control group were observed regarding adverse reaction, surgical complication and disease progression. Our results show that adding PD-1 blockade after neoadjuvant chemoradiation increases the pCR rate for patients with LARC and raises no substantial safety concerns. Phase 3 trials with larger sample sizes are warranted (ClinicalTrials.gov identifier NCT05245474). |
| Database: |
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