Single-center phase 2 trial of total neoadjuvant therapy with PD-1 blockade for high-risk proficient mismatch repair rectal cancer

Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer (LARC), especially for patients with high-risk factors. The efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) LARC is unknown. A phase 2 trial at Peking University Cancer Hospital & Institute (Beijing, China) evaluated TNT with induction chemoimmunotherapy followed by long-course chemoradiation among 25 patients with high-risk pMMR LARC. Twenty-two patients completed the TNT schedule. The pathologic complete response rate was 33.3%, while 48% achieved clinical complete response. R0 resection was achieved in 21 of 21 patients. The most common adverse event was nausea (80% of patients); grade 3 toxic effects occurred in 36%. The authors conclude that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk pMMR LARC.