KEY TAKEAWAYS
- The phase 3 ORIENT-15 trial aimed to compare the efficacy of sintilimab with a placebo when used as first-line therapy for patients.
- The study enrolled 659 adults with locally advanced or metastatic oesophageal squamous cell cancer without prior systemic therapy.
- Patients who received sintilimab in combination with chemotherapy had significantly better overall survival and progression-free survival than those who received a placebo and chemotherapy.
- Patients with a combined positive score of ten or higher had a significantly longer overall survival when treated with sintilimab plus chemotherapy.
- The study concluded that sintilimab has similar advantages to cisplatin with 5-fluorouracil and is an effective first-line therapy for patients with unresectable locally progressed
This study aims to compare the efficacy of sintilimab with a placebo when used as first-line therapy for patients with unresectable locally progressed, recurring, or metastatic oesophageal squamous cell carcinoma. A total of 659 adults (18 years old) with locally advanced or metastatic oesophageal squamous cell cancer and no prior systemic therapy were enrolled. Patients received cisplatin 75 mg/m2 with paclitaxel 175 mg/m2 every 3 weeks in addition to sintilimab (3 mg/kg in patients weighing 60 kg or 200 mg in patients weight 60 kg) per a 1:1 randomization. Both cisplatin and paclitaxel and cisplatin and 5-fluorouracil (800 mg/m2 continuous infusion on days 1–5) are now options in the experiment, with the latter being chosen by the investigators. Six hundred and fifty-nine patients were randomly assigned to receive either sintilimab (n=327) or placebo (n=332) in addition to chemotherapy.
Overall survival was measured for both groups. Sintilimab or a placebo was given to 616 of 659 patients (93%) who also received cisplatin and paclitaxel and to 43 of 659 patients (7%) who also received cisplatin and 5-fluorouracil. Overall, patients who received sintilimab in combination with chemotherapy fared better than those who received placebo and chemotherapy at the time of the interim analysis (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P=0.001), as did those who had a combined positive score of ten or higher (median 17.2 v 13.2 months, hazard ratio 0.64, 0.48 to 0.85, P=0.002). Patients with cumulative positive ratings of 10 had a substantially longer progression-free survival when treated with sintilimab plus chemotherapy than those treated with placebo and chemotherapy (median 8.3 months vs 5.7 months; HR 0.56; 95% CI 0.46 to 0.68; P<0.001). 321 of 327 patients (98%) in the sintilimab-chemotherapy group and 326 of 332 patients (98%) in the placebo-chemotherapy group experienced treatment-related adverse events. In the sintilimab-chemotherapy group, 60% (196/327) and 55% (181/332) of patients experienced treatment-related side events of grade 3. Patients with advanced or metastatic oesophageal squamous cell carcinoma who received sintilimab in combination with cisplatin + paclitaxel had significantly better overall survival and progression-free survival than those who received a placebo. Sintilimab has similar advantages to cisplatin with 5-fluorouracil.
Source:https://pubmed.ncbi.nlm.nih.gov/35440464/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03748134
Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, Wang B, Sun G, Ji Y, Cao G, Liu H, Cui T, Li N, Qiu W, Li G, Hou X, Luo H, Xue L, Zhang Y, Yue W, Liu Z, Wang X, Gao S, Pan Y, Galais MP, Zaanan A, Ma Z, Li H, Wang Y, Shen L; 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. doi 10.1136/bmj-2021-068714. PMID: 35440464; PMCID: PMC9016493.
