Durvalumab联合或不联合Tremelimumab联合化疗一线治疗转移性NSCLC

3期POSEIDON研究的主要分析表明(所有组的中位随访时间为34.9个月)，在EGFR/ ALK野生型转移性NSCLC (mNSCLC)患者中，一线tremelimumab + durvalumab和化疗(T+D+CT)与CT相比，总生存期(OS)有统计学显著改善。与CT相比，D+CT有改善OS的趋势，但未达到统计学差异。本文报告了长期随访(中位>5年)后的OS分析。

1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell (TC) PD-L1 expression (≥50% vs <50%), disease stage (IVA vs IVB), and histology (squamous vs nonsquamous). Serious adverse events were collected during follow-up.

1,013例患者被随机分组(1∶1∶1)，分别接受T+D+CT、D+CT或CT治疗，并根据肿瘤细胞(TC) PD-L1表达(≥50% vs <50%)、疾病分期(IVa VS IVb)和组织学(鳞状vs非鳞状)进行分层。随访期间收集严重不良事件。

After median follow-up of 63.4 months across all arms, T+D+CT showed sustained OS benefit versus CT (hazard ratio [HR] 0.76, 95% CI: 0.64–0.89; 5-year OS: 15.7% vs 6.8%). OS improvement with D+CT versus CT (HR 0.84, 95% CI: 0.72–1.00; 5-year OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR 0.69, 95% CI: 0.56–0.85) versus squamous (HR 0.85, 95% CI: 0.65–1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 TC <1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified.

所有组的中位随访时间为63.4个月，与CT相比，T+D+CT显示出持续的OS获益(风险比[HR] 0.76, 95% CI: 0.64 ~ 0.89;5年OS: 15.7% vs 6.8%)。D+CT与CT相比，OS改善与初步分析一致(HR 0.84, 95% CI: 0.72 ~ 1.00;5年OS: 13.0%)。与CT相比，T+D+CT的OS获益在非鳞状(HR 0.69, 95% CI: 0.56 ~ 0.85)相比鳞状(HR 0.85, 95% CI: 0.65 ~ 1.10) mNSCLC中仍然更明显。无论PD-L1表达情况如何(包括PD-L1 TC <1%的患者)，T+D+CT与CT相比的OS获益仍然明显，并且在STK11突变型(非鳞状)、KEAP1突变型和kras突变型(非鳞状)mNSCLC中仍然明显。未发现新的安全性信号。

After median follow-up of >5 years, T+D+CT showed durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease.

在中位随访5年后，T+D+CT与CT相比显示出持久的长期OS获益，支持将其作为mNSCLC的一线治疗，包括患有更难治疗的疾病的患者亚组。