Use of total neoadjuvant therapy for locally advanced rectal cancer

This open-label, phase 2, randomized clinical trial (NRG-GI002) was conducted to determine if the addition of pembrolizumab during and after neoadjuvant chemoradiotherapy can result in an improvement in the neoadjuvant rectal (NAR) score relative to treatment with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and chemoradiotherapy alone, in patients suffering from locally advanced rectal cancer (LARC). Patients were randomly assigned (1:1) to neoadjuvant FOLFOX for 4 months and then were administered chemoradiotherapy (capecitabine with 50.4 Gy) with or without intravenous pembrolizumab given at a dosage of 200 mg every 3 weeks for up to 6 doses prior to surgery. The mean (SD) NAR score for the pembrolizumab arm (PA) vs for control arm (CA) was 11.53 (12.43) vs 14.08 (13.82), respectively. The pathologic complete response rate was estimated to be 31.9% in the PA vs 29.4% in the CA. Findings indicate safety of pembrolizumab added to chemoradiotherapy as part of total neoadjuvant therapy, however, further study is not supported owing to the observed difference in the NAR score.