Solange Peters, Byoung Chul Cho, Alexander V Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Konstantin Laktionov, Dmytro Trukhin, Sang-We Kim, Grygorii M Ursol, Maen Hussein, Farah Louise Lim, Cheng-Ta Yang, Luiz Henrique Araujo, Haruhiro Saito, Niels Reinmuth, Caitlin Lowery, Helen Mann, Ross Stewart, Haiyi Jiang, Edward B Garon, Tony Mok, Melissa L Johnson
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This paper reports prespecified OS analyses after longer-term follow-up (median >5 years).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes from the Phase 3 POSEIDON Trial.\",\"authors\":\"Solange Peters, Byoung Chul Cho, Alexander V Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Konstantin Laktionov, Dmytro Trukhin, Sang-We Kim, Grygorii M Ursol, Maen Hussein, Farah Louise Lim, Cheng-Ta Yang, Luiz Henrique Araujo, Haruhiro Saito, Niels Reinmuth, Caitlin Lowery, Helen Mann, Ross Stewart, Haiyi Jiang, Edward B Garon, Tony Mok, Melissa L Johnson\",\"doi\":\"10.1016/j.jtho.2024.09.1381\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The primary analysis (median follow-up 34.9 months across all arms) of the phase 3 POSEIDON study demonstrated a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR/ALK-wild-type metastatic NSCLC (mNSCLC). 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引用次数: 0
摘要
简介POSEIDON三期研究的主要分析(所有研究臂的中位随访时间为34.9个月)显示,在表皮生长因子受体(EGFR)/ALK-wild型转移性非小细胞肺癌(mNSCLC)患者中,一线曲妥珠单抗加杜伐单抗和化疗(T+D+CT)与CT相比,总生存期(OS)的改善具有统计学意义。D+CT与CT相比,OS有改善趋势,但未达到统计学意义。方法:将1013例患者随机(1:1:1)分为T+D+CT、D+CT或CT,并根据肿瘤细胞(TC)PD-L1表达量(≥50% vs 结果)进行分层:所有治疗方案的中位随访时间均为63.4个月,T+D+CT与CT相比具有持续的OS优势(危险比[HR]0.76,95% CI:0.64-0.89;5年OS:15.7% vs 6.8%)。D+CT对CT的OS改善(HR 0.84,95% CI:0.72-1.00;5年OS:13.0%)与主要分析结果一致。在非鳞癌(HR 0.69,95% CI:0.56-0.85)与鳞癌(HR 0.85,95% CI:0.65-1.10)mNSCLC中,T+D+CT与CT相比的OS获益仍然更为明显。无论PD-L1表达如何,包括PD-L1 TC患者,T+D+CT相对于CT的OS获益仍然明显:在中位随访超过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,包括在较难治疗的患者亚群中。
Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes from the Phase 3 POSEIDON Trial.
Introduction: The primary analysis (median follow-up 34.9 months across all arms) of the phase 3 POSEIDON study demonstrated a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR/ALK-wild-type metastatic NSCLC (mNSCLC). D+CT showed a trend for OS improvement versus CT that did not reach statistical significance. This paper reports prespecified OS analyses after longer-term follow-up (median >5 years).
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍:
Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.