AUTHOR=Zhou Yi-Xin , Chen Ping , Sun Yu-Ting , Zhang Bei , Qiu Miao-Zhen 

TITLE=Comparison of PD-1 Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma in the Second-Line Setting

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.698732

DOI=10.3389/fonc.2021.698732

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>KEYNOTE-181, ATTRACTION-3, and ESCORT trials have opened the era of programmed death 1 (PD-1) inhibitors in the second-line therapy for esophageal squamous cell carcinoma (ESCC). There is no head-to-head comparison of pembrolizumab <italic>vs.</italic> nivolumab <italic>vs.</italic> camrelizumab in the second-line setting for ESCC. We performed an indirect comparison to explore the optimal choice of immune checkpoint inhibitor (ICI) for advanced ESCC.</p></sec><sec><title>Methods</title><p>Patients in ATTRACTION-3 and ESCORT were all squamous carcinoma, while KEYNOTE-181 enrolled both adenocarcinoma and squamous carcinoma patients. We only extract information of patients with squamous carcinoma from KEYNOTE 181 study and all the patients from ATTRACTION-3 and ESCORT. The main clinical outcomes for this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs).</p></sec><sec><title>Results</title><p>Indirect analysis showed similar survival benefit among three PD-1 inhibitors. Nivolumab was comparable with pembrolizumab in most subgroups except that nivolumab was slightly better for patients with performance status (PS) score of 1 [HRnivo/pembro: 0.68 (95% confidence interval (CI): 0.45–1.02], <italic>p</italic> = 0.07). Compared with nivolumab indirectly, pembrolizumab and camrelizumab had better PFS [HRpembro/nivo: 0.85 (95% CI: 0.63–1.14), <italic>p</italic> = 0.29; HRcam/nivo: 0.64 (95% CI: 0.47–0.87), <italic>p</italic> = 0.004] and significantly higher ORR [RRpembro/nivo: 2.51 (95% CI: 1.22–5.15), <italic>p</italic> = 0.01; RRcam/nivo: 3.52 (95% CI: 1.73–7.18), <italic>p</italic> = 0.001]. Compared with camrelizumab indirectly, pembrolizumab had slightly worse PFS [HRpembro/cam: 1.33 (95% CI: 0.99–1.79), <italic>p</italic> = 0.057] and comparable ORR [RRpembro/cam: 0.71 (95% CI: 0.32–1.60; <italic>p</italic> = 0.41)]. Camrelizumab had a significantly higher rate of all grade TRAEs than both pembrolizumab and nivolumab.</p></sec><sec><title>Conclusions</title><p>Combining the safety and potential survival benefit, we recommend nivolumab for ESCC patients with PS score of 1 and pembrolizumab or camrelizumab for patients with better PS and seeking for higher efficacy or longer PFS.</p></sec>