新辅助PD-1抑制剂(Sintilimab)在非小细胞肺癌中的3年随访结果

SCI

11 June 2022

Three-year Follow-up of Neoadjuvant PD-1 inhibitor (Sintilimab) in Non-Small Cell Lung Cancer 

(JTO, IF:15.6)

• Zhang F, Guo W, Zhou B, Wang S, Li N, Qiu B, Lv F, Zhao L, Li J, Shao K,Xue Q, Gao S, He J, Research article: Three-year Follow-up of Neoadjuvant PD-1 inhibitor (Sintilimab)in Non-Small Cell Lung Cancer, Journal of Thoracic Oncology (2022), doi: https://doi.org/10.1016/j.jtho.2022.04.012.

Background 背景

Programmed death receptor-1 (PD-1) inhibitors have been proved to be feasible  and  efficacy  in  multiple  cancers,  including  non-small  cell  lung  cancer (NSCLC). But few studies have evaluated the effectiveness  of PD-1  inhibitor as neoadjuvant therapy with a long-term follow-up. Here, in this phase 1b study witha 3-year follow-up, we reported the clinical outcomes of patients who received the PD-1 inhibitor as neoadjuvant therapy.

程序性死亡受体-1 (PD-1)抑制剂已被证明在多种癌症中是可行和有效的，包括非小细胞肺癌(NSCLC)。但很少有研究通过长期随访评估PD-1抑制剂作为新辅助治疗的有效性。在这项为期3年的1期临床研究中，我们报道了接受PD-1抑制剂作为新辅助治疗的患者的临床结果。

  Methods 方法

Two doses of sintilimab(intravenously, 200 mg)were used for patients with stage IA-IIIB NSCLC(registration number: ChiCTR-OIC-17013726). Then surgery was performed within 29 to 43 days after the first dose. And all patients underwent positron  emission  tomography–computed  tomography  (PET-CT) at  enrollment  and before surgery to evaluate tumor metabolism after administration of PD-1 inhibitor. We also  evaluated the expression  of  programmed  cell  death  ligand  1(PD-L1) as  an exploratory analysis in 32 eligible patients.Safety was the primary endpoint. Overall survival (OS), disease-free survival (DFS), event survival (EFS), and major pathologic response (MPR) were the key secondary endpoints. 

对IA-IIIB期NSCLC(注册号:ChiCTR-OIC-17013726)患者给予两剂西替单抗(静脉注射，200 mg)。第一次服药后29 ~ 43天内进行手术。所有患者在入组时和手术前都接受了正电子发射断层扫描-计算机断层扫描(PET-CT)，以评估PD-1抑制剂治疗后的肿瘤代谢。我们还对32例符合条件的患者进行了探索性分析，评估了程序性细胞死亡配体1(PD-L1)的表达。安全性是主要终点。总生存期(OS)、无病生存期(DFS)、事件生存期(EFS)和主要病理缓解期(MPR)是关键的次要终点。

Results 结果

With the mean 37.8 months follow-up, 3-year OS rates were 88.5% and the 3-year DFS rate was 75.0% among patients who underwent R0 resection. In patients with positive  PD-L1  expression, 3-year  OS and  DFS rates were 95.5% and 81.8%, respectively.Eight  patients  had  recurrent  tumors,  including  local  recurrence,  lung metastasis, brain metastasis and bone metastasis. Patients with PD-L1 ≥1% had more favorable clinical outcomes than the other subgroup(HR, 0.275;95% CI,0.078 to 0.976). No more new adverse events (AEs) have occurred in the 3-year follow-up since we first reported them in the former publication.

平均随访37.8个月，R0切除术患者3年OS率为88.5%，3年DFS率为75.0%。PD-L1表达阳性的患者，3年OS和DFS分别为95.5%和81.8%。8例患者肿瘤复发，包括局部复发、肺转移、脑转移和骨转移。PD-L1≥1%的患者比其他亚组有更有利的临床结局(HR, 0.275;95% CI,0.078 - 0.976)。自我们在以前的出版中首次报道以来，在3年的随访中没有再发生新的不良事件(AE)。

Conclusions 结论

This is the first study to report the long-term survival probability of NSCLC patients receiving PD-1inhibitors as the neoadjuvant treatment. The three-year follow-up revealed that  patients  with  positive  PD-L1  expression  and  high  tumor mutation burden have favorable clinical outcomes.

这是第一个报道PD-1抑制剂作为新辅助治疗的NSCLC患者的长期生存概率的研究。3年随访显示PD-L1表达阳性、肿瘤突变负担高的患者具有良好的临床预后。