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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Johnson","doi":"10.1016/j.cllc.2024.03.003","DOIUrl":null,"url":null,"abstract":"<div><p></p><ul><li><span>•</span><span><p>In the phase 3 POSEIDON study, patients with <em>EGFR/ALK</em> 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.</p></span></li><li><span>•</span><span><p>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.</p></span></li><li><span>•</span><span><p>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.</p></span></li><li><span>•</span><span><p>Here we report outcomes from POSEIDON from post-hoc exploratory analyses in subgroups with PD-L1 TC ≥ 1% versus < 1%.</p></span></li><li><span>•</span><span><p>Among 1012/1013 randomized patients with known PD-L1 status, 644 (63.6%) versus 368 (36.4%) had PD-L1 TC ≥ 1% versus < 1%.</p></span></li><li><span>•</span><span><p>Both T + D + CT and D + CT appeared to show OS/PFS benefit versus CT in patients with PD-L1 TC ≥ 1%.</p></span></li><li><span>•</span><span><p>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.</p></span></li><li><span>•</span><span><p>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%.</p></span></li></ul></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 3","pages":"Pages 266-273.e5"},"PeriodicalIF":3.3000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152573042400038X/pdfft?md5=74f2cabd13240bb3ada54b4f21c1d1d1&pid=1-s2.0-S152573042400038X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Edward B. 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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%.
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.