1. Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.
- Author
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Xiao WW, Chen G, Gao YH, Lin JZ, Wu XJ, Luo HL, Lu ZH, Wang QX, Sun R, Cai PQ, Zhu CM, Liu M, Li JB, Wang YR, Jin Y, Wang F, Luo HT, Li CL, Pan ZZ, and Xu RH
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, DNA Mismatch Repair, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors administration & dosage, Chemoradiotherapy methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Rectal Neoplasms therapy, Rectal Neoplasms immunology, Rectal Neoplasms pathology, Rectal Neoplasms drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Neoadjuvant Therapy methods
- 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., Competing Interests: Declaration of interests H.-T.L. and C.-L.L. are employed by YuceBio Technology Co., Ltd. R.-H.X. has served as a consulting or advisory role for Bristol-Myers Squibb, Merck Serono, Roche, Astellas, and AstraZeneca., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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