A Brief Report of Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: Outcomes by Tumor PD-L1 Expression in the Phase 3 POSEIDON Study

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-05-01 DOI:10.1016/j.cllc.2024.03.003

Edward B. Garon , Byoung Chul Cho , Alexander Luft , Jorge Alatorre-Alexander , Sarayut Lucien Geater , Dmytro Trukhin , Sang-We Kim , Grygorii Ursol , Maen Hussein , Farah Louise Lim , Cheng-Ta Yang , Luiz Henrique Araujo , Haruhiro Saito , Niels Reinmuth , Milena Kohlmann , Caitlin Lowery , Helen Mann , Solange Peters , Tony S. Mok , Melissa L. Johnson

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Abstract

•
In the phase 3 POSEIDON study, patients with EGFR/ALK wild-type metastatic NSCLC (mNSCLC) were randomized (1:1:1) to first-line tremelimumab plus durvalumab and platinum-based chemotherapy (T + D + CT), durvalumab plus chemotherapy (D + CT), or chemotherapy alone (CT), with stratification by programmed cell death ligand-1 (PD-L1) tumor cell (TC) expression level (≥ 50% vs. < 50%), disease stage, and histology.
•
In alpha-controlled analyses in the ITT population, T + D + CT significantly improved overall survival (OS) and progression-free survival (PFS) versus CT, leading to approval for this regimen. PFS was also significantly improved with D + CT versus CT; a trend for improved OS did not reach statistical significance.
•
Patients with PD-L1-low or -negative tumors may show primary resistance to anti-PD-(L)1 therapy, with real-world data suggesting that treatment benefits observed in trials do not always translate into optimal outcomes in clinical practice.
•
Here we report outcomes from POSEIDON from post-hoc exploratory analyses in subgroups with PD-L1 TC ≥ 1% versus < 1%.
•
Among 1012/1013 randomized patients with known PD-L1 status, 644 (63.6%) versus 368 (36.4%) had PD-L1 TC ≥ 1% versus < 1%.
•
Both T + D + CT and D + CT appeared to show OS/PFS benefit versus CT in patients with PD-L1 TC ≥ 1%.
•
Consistent with the role of cytotoxic T-lymphocyte-associated antigen 4 and PD-L1 in the immune response, the addition of tremelimumab to first-line durvalumab and chemotherapy also conferred clinical benefit to patients with PD-L1 TC < 1% mNSCLC.
•
This exploratory subgroup analysis of POSEIDON supports T + D + CT as a first-line treatment option for patients with mNSCLC irrespective of PD-L1 expression, including the harder-to-treat subgroup with PD-L1 TC < 1%.

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关于Durvalumab与Tremelimumab或不与Tremelimumab联合化疗作为转移性非小细胞肺癌一线疗法的简要报告：3期POSEIDON研究中根据肿瘤PD-L1表达得出的疗效

在3期POSEIDON研究中，在转移性NSCLC（mNSCLC）患者中，一线tremelimumab+durvalumab和铂类化疗（T+D+CT）与单纯化疗（CT）相比，能显著改善总生存期（OS；危险比[HR]0.77[95%置信区间{CI}0.65-0.92]；=.0030）和无进展生存期（PFS），从而使该方案获得批准。我们根据程序性细胞死亡配体-1（PD-L1）肿瘤细胞（TC）的表达水平来报告疗效。野生型mNSCLC患者随机（1:1:1）接受T+D+CT、度伐单抗加化疗（D+CT）或CT治疗，并根据PD-L1表达（TC≥50% vs <50%）、疾病分期和组织学进行分层。在这项事后探索性分析中，对PD-L1 TC≥1%与<1%亚组的OS、PFS、客观反应率、反应持续时间和安全性进行了评估。在1012/1013例已知PD-L1状态的随机患者中，644例（63.6%）与368例（36.4%）TC≥1%与<1%。在两个亚组中，T+D+CT与CT相比，OS（TC≥1%，0.76 [0.61-0.95]；<1%，0.77 [0.58-1.00]）和PFS（TC≥1%，0.68 [0.54-0.85]；<1%，0.78 [0.59-1.03]）均有数值上的改善（HR [95% CI]）。在TC≥1%的亚组（0.79 [0.64-0.98]），D+CT与CT相比显示出数值上的OS改善，但在＜1%的亚组（0.99 [0.76-1.30]），D+CT与CT相比未显示出数值上的OS改善，PFS结果相似。两个亚组的安全性与总体人群一致。这项探索性分析支持T+D+CT作为mNSCLC患者的一线治疗方案，无论PD-L1表达如何，包括PD-L1 TC<1%的难治亚组，这与细胞毒性T淋巴细胞相关抗原4和PD-L1在免疫反应中的作用一致。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567