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

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer 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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引用次数: 0

摘要

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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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

•
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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来源期刊

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.