Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial

Mené sur 186 patients atteints d'un cancer rectal localement avancé, cet essai randomisé multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse pathologique complète, d'un traitement associant une radiothérapie et des inhibiteurs de point de contrôle immunitaire

Résumé en anglais

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).