Xiao et al. report the safety and efficacy of adding sintilimab (anti-PD-1) to neoadjuvant chemoradiotherapy for patients with mismatch repair-proficient locally advanced rectal cancer, based on a phase 2 randomized clinical trial. Adding sintilimab to neoadjuvant chemoradiotherapy significantly increased the complete response rate from 26.9% to 44.8%. Patients with a PD-L1 combined positive score ≥ 2 had a CR rate of 53.8% in the experimental arm compared to 23.7% in the control arm, indicating a significant benefit from sintilimab in patients with higher PD-L1 expression. The combination therapy had a manageable safety profile.
Contributed by Shishir Pant
ABSTRACT: Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.
Author Info: (1) Department of Radiation Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for C
Author Info: (1) Department of Radiation Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China; United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd, Guangzhou, China.(2) Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.(3) Department of Radiation Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.(4) Department of Radiology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.(5) Department of Pathology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.(6) Department of Ultrasound, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
(7) Department of Statistics, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China. (8) Department of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China. (9) Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, China. (10) Department of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China. Electronic address: xurh@sysucc.org.cn.
