Every three weeks, all patients received sintilimab or placebo combined with chemotherapy. The chemotherapy regimen was chosen by the investigator: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil. Sintilimab or placebo was given intravenously at a dose of 3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg on day 1 of each cycle. Cisplatin (75 mg/m2 on day 1 of each cycle) plus paclitaxel (87.5 mg/m2 on day 1 and day 8 of cycle 1; 175 mg/m2 on day 1 of the other cycles) or 5-fluorouracil (800 mg/m2 continuous administration on days 1-5 of each cycle) were also given intravenously. A maximum of six cycles was recommended for chemotherapy. Treatment with sintilimab or placebo was continued until progressive disease, intolerable toxicity, the start of new antitumour treatment, withdrawal of consent, lost to follow-up, death, completion of treatment, or any other reasons determined by the investigators for stopping treatment, whichever occurred first.
Sintilimab or placebo was continued for a maximum of 24 months. Sintilimab or placebo was used alone if chemotherapy was intolerable, or when six cycles of chemotherapy had been given. The choice of chemotherapy regimen (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) could not be switched during the study. Appendix 2 provides more details of the study design.
Assessments of the tumours were performed by the investigators according to RECIST version 1.1 at baseline, once every six weeks for 48 weeks, and then once every 12 weeks. Adverse events were assessed up to 90 days after the last dose and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Survival was assessed every 60 days during follow-up.
Expression of PD-L1 in fresh or archival tumour sample was assessed during screening at a central laboratory (Covance, Shanghai, China) with the PD-L1 immunohistochemistry 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA). The combined positive score was defined as the number of PD-L1 staining cells (tumour cells, lymphocytes, and macrophages) divided by the total number of viable tumour cells. The tumour proportion score was defined as the percentage of viable tumour cells showing partial or complete membrane staining.
Sintilimab or placebo was continued for a maximum of 24 months. Sintilimab or placebo was used alone if chemotherapy was intolerable, or when six cycles of chemotherapy had been given. The choice of chemotherapy regimen (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) could not be switched during the study. Appendix 2 provides more details of the study design.
Assessments of the tumours were performed by the investigators according to RECIST version 1.1 at baseline, once every six weeks for 48 weeks, and then once every 12 weeks. Adverse events were assessed up to 90 days after the last dose and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Survival was assessed every 60 days during follow-up.
Expression of PD-L1 in fresh or archival tumour sample was assessed during screening at a central laboratory (Covance, Shanghai, China) with the PD-L1 immunohistochemistry 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA). The combined positive score was defined as the number of PD-L1 staining cells (tumour cells, lymphocytes, and macrophages) divided by the total number of viable tumour cells. The tumour proportion score was defined as the percentage of viable tumour cells showing partial or complete membrane staining.
