Multicenter randomized phase 2 trial of immunotherapy-based total neoadjuvant therapy for pMMR/MSS locally advanced rectal cancer

The multicenter randomized phase 2 TORCH trial in China evaluated immunotherapy-based total neoadjuvant therapy (iTNT) for proficient mismatch repair of microsatellite stable locally advanced rectal cancer (pMMR/MSS LARC). Patients were randomized to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy (with capecitabine and oxaliplatin and toripalimab) or to group B for two cycles of induction immunotherapy followed by SCRT and four cycles of immunotherapy. After the neoadjuvant therapy patients underwent mesorectal excision or watch-and-wait (WW) based on tumor response. Complete response was achieved in 56.5% in group A and 54.2% in group B (both groups p<0.001 versus historical data of 25% after conventional TNT). Twenty-five percent of patients in each group underwent WW and remained disease-free. The most-frequent grade 3 or 4 toxicity were thrombocytopenia and neutropenia. Patients in group A had higher rate of clinical complete response at restaging (43.5% versus 35.6%) and lower rate of grade 3 or 4 thrombocytopenia (24.2% versus 33.9% during neoadjuvant treatment. The authors conclude that both iTNT regimens improved CR rates in pMMR/MSS LARC compared with historical data with acceptable toxicity.