PD-L1 overexpression was observed in up to 40% of ESCC 10. The results from these trials and the fact that advanced or metastatic ESCC progresses rapidly prompted us to modify the dose frequency to every 2 weeks to increase the possibility of improving efficacy.Īdvances in immunotherapy have uncovered programmed cell death protein ligand 1 (PD-L1) as a potential therapeutic target and biomarker for patients with ESCC. A few randomized trials have demonstrated that survival of patients receiving chemotherapy regimens with shortened intervals between cycles was better than that of patients treated by standard chemotherapy in ovarian cancer, breast cancer and advanced colorectal cancer 7, 8, 9. In these trials, chemotherapy was administered every 3 or 4 weeks. Although 5-fluorouracil (5-FU) or paclitaxel plus cisplatin has been widely used in the first-line setting, programmed cell death protein 1 (PD-1) inhibitors in combination with chemotherapy showed improved efficacy compared with chemotherapy alone in phase 3 trials 2, 3, 4, 5, 6. Systemic chemotherapy remains the backbone of treatment of unresectable or metastatic ESCC. Therefore, there is an unmet need for new antitumor agents and therapeutic strategies for advanced ESCC. Despite progress in chemotherapy for patients with unresectable or metastatic ESCC, the overall outcome remains poor, with median overall survival (OS) of 10–12 months (refs. This study is registered with ( NCT03958890).Įsophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer and accounts for approximately 84% of all esophageal cancer cases 1. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively hazard ratio, 0.68 95% confidence interval, 0.53–0.87 P = 0.0020). At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively hazard ratio, 0.60 95% confidence interval, 0.48–0.75 P < 0.0001). In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m 2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m 2) (on days 1 and 2), once every 2 weeks. First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited.
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