Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649.

patients_and_methods

Adults with previously untreated, non-human epidermal growth factor receptor 2-positive, unresectable, advanced or metastatic gastroesophageal adenocarcinoma were randomized to receive nivolumab plus chemotherapy (n = 789) or chemotherapy (n = 792).

之前未接受治疗的、非人类表皮生长因子受体2阳性的、无法切除的、晚期或转移性胃食管腺癌患者被随机分为两组，一组接受纳武利尤单抗加化疗（n = 789），另一组仅接受化疗（n = 792）。

Primary endpoints were met and reported previously, with nivolumab plus chemotherapy demonstrating superior overall survival(OS) and progression-free survival(PFS) versus chemotherapy in patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥5.

主要终点已达成并已报告，与化疗相比，纳武利尤单抗联合化疗在程序性死亡配体1（PD-L1）联合阳性评分（CPS）≥5的患者中显示出更优越的总生存（OS）和无进展生存（PFS）。

Results

With a minimum follow-up of 60.1 months, the OS benefit [hazard ratio(HR) 0.71, 95% confidence interval(CI) 0.61-0.81] and PFS benefit (HR 0.71, 95% CI 0.61-0.82) with nivolumab plus chemotherapy versus chemotherapy in patients with PD-L1 CPS ≥5 were sustained.

在至少60.1个月的随访期间，纳武利尤单抗联合化疗与化疗相比，在PD-L1 CPS≥5的患者中，总生存（OS）获益（风险比[HR] 0.71，95%置信区间[CI] 0.61-0.81）和无进展生存（PFS）获益（HR 0.71，95% CI 0.61-0.82）持续存在。

Five-year OS and PFS rates were 16% versus 6% and 10% versus 6%, respectively.

五年总生存（OS）和无进展生存（PFS）率分别为16%对6%和10%对6%。

Objective response rateper blinded independent central review was 58% (95% CI 54% to 62%) versus 46% (95% CI 42% to 50%), and median duration of response was 8.5 months (95% CI 7.7-9.9 months) versus 6.9 months (95% CI 5.9-7.6 months), respectively.

根据盲法独立中心评审，客观缓解率为58%（95%置信区间54%至62%）对比46%（95%置信区间42%至50%），且缓解的中位持续时间为8.5个月（95%置信区间7.7-9.9个月）对比6.9个月（95%置信区间5.9-7.6个月）。

Survival and response benefits were also maintained in patients with PD-L1 CPS ≥1, patients with PD-L1 CPS ≥10, and all randomized patients.

在 PD-L1 CPS ≥1 的患者中，PD-L1 CPS ≥10 的患者中，以及所有随机化患者中，生存和反应益处也得到了维持。

Grade 3/4 treatment-related adverse events occurred in 60% of patients receiving nivolumab plus chemotherapy and 45% of patients receiving chemotherapy.

接受纳武利尤单抗加化疗的患者中有60%出现了3/4级治疗相关不良事件，而仅接受化疗的患者中这一比例为45%。

No new safety concerns were observed.

未观察到新的安全问题。

Conclusions

To our knowledge, these are the first reported 5-year results of a programmed cell death protein 1 inhibitor plus chemotherapy in gastroesophageal adenocarcinoma.

据我们所知，这些是首次报告的关于程序性细胞死亡蛋白1抑制剂联合化疗在胃食管腺癌中5年结果的研究。

Nivolumab plus chemotherapy continued to demonstrate long-term survival benefit and acceptable safety after 5 years of follow-up, reinforcing its use as a standard first-line treatment for PD-L1-positive patients.

Nivolumab联合化疗在5年的随访后继续显示出长期生存益处和可接受的安全性，这进一步巩固了其作为PD-L1阳性患者标准一线治疗的地位。