The first-line treatment with sintilimab plus chemotherapy significantly improves the overall survival (OS) and progression-free survival (PFS) in patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC).
The current standard of care for advanced or metastatic OSCC patients is limited to platinum-based chemotherapies. Recently, immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have shown clinical benefits in several tumour types. Therefore, the efficacy of combining sintilimab (anti-PD-L1 antibody) with chemotherapy for OSCC patients was evaluated in the ORIENT-15 trial.
The multicentre, double-blind, phase-3, ORIENT-15 clinical trial enrolled 659 adults (aged ≥18 years) with advanced or metastatic OSCC who had not received systemic treatment from 66 sites in China and 13 sites outside China. All the participants were randomised (1:1) to either receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) plus chemotherapy (cisplatin 75 mg/m2 plus paclitaxel 175 mg/m2 every three weeks). The study’s primary endpoint was OS and in patients with combined positive scores of ≥10 for expression of PD-L-1.
In the interim analysis, sintilimab plus chemotherapy significantly improved the OS (16.7 months) than placebo control (12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001). This clinical benefit was also observed in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Similar improvement was seen in PFS with sintilimab vs placebo (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Treatment-related grade ≥3 events were observed in 60% and 55% of patients in the sintilimab and placebo groups.
The results from the ORIENT-15 study show the promising clinical benefit of combining sintilimab with chemotherapy for patients with advanced or metastatic OSCC.
Lu Z, Wang J, Shu Y, Liu L, et al.; ORIENT-15 study group. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022 Apr 19;377:e068714