David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Yonsei Cancer Center, Seoul, Republic of Korea.
Lung Cancer. 2023 Dec;186:107422. doi: 10.1016/j.lungcan.2023.107422. Epub 2023 Nov 11.
In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs).
Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression.
972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1.
Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC.
在 3 期 POSEIDON 研究中，一线替西木单抗联合度伐利尤单抗和化疗显著改善了转移性非小细胞肺癌（NSCLC）患者的总生存期和无进展生存期，优于化疗。我们报告了患者报告的结局（PRO）。
未经治疗的患者按 1:1:1 随机分为替西木单抗联合度伐利尤单抗和化疗、度伐利尤单抗联合化疗和化疗组。采用欧洲癌症研究与治疗组织（EORTC）30 项核心生活质量问卷（QLQ-C30）及其 13 项肺癌模块（QLQ-LC13）评估 PRO（预设次要终点）。我们通过对数秩检验分析了从随机分组到症状、功能和总体健康状况/生活质量（QoL）恶化的时间（TTD），并通过逻辑回归分析了改善率。
972/1013（96%）例随机患者完成了基线 QLQ-C30 和 QLQ-LC13 问卷，各治疗组之间的评分具有可比性。与化疗相比，接受替西木单抗联合度伐利尤单抗和化疗的患者所有 PRO 项目的 TTD 中位数更长。除腹泻外，替西木单抗联合度伐利尤单抗和化疗的 TTD 风险比均有利于替西木单抗联合度伐利尤单抗和化疗；95%置信区间（CI）均未跨越 1.0，提示总体健康状况/QoL、身体功能、认知功能、疼痛、恶心/呕吐、失眠、便秘、咯血、呼吸困难和其他部位疼痛。对于度伐利尤单抗联合化疗，除恶心/呕吐和腹泻外，所有项目的 TTD 中位数均长于化疗。除食欲减退外，度伐利尤单抗联合化疗的 TTD 风险比均有利于度伐利尤单抗联合化疗；95%CI 均未跨越 1.0，提示总体健康状况/QoL、身体功能、角色功能、呼吸困难和其他部位疼痛。对于免疫治疗联合化疗组，与化疗相比，所有 PRO 项目的改善率均较高，优势比（OR）>1。
与化疗相比，替西木单抗联合度伐利尤单抗和化疗可延缓症状、功能和总体健康状况/QoL 的恶化。这些结果与生存的显著改善一起，支持替西木单抗联合度伐利尤单抗和化疗作为转移性 NSCLC 的一线治疗选择。
