David Geffen School of Medicine, University of California/TRIO-US Network, Los Angeles, CA.
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
Clin Lung Cancer. 2021 Jul;22(4):301-312.e8. doi: 10.1016/j.cllc.2021.02.010. Epub 2021 Feb 19.
The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs).
Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests.
There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (-9.5; 99% confidence interval [CI], -17.0 to -2.0), durvalumab + tremelimumab (-11.7; 99% CI, -19.4 to -4.1); and for C30 appetite loss: durvalumab (-11.9; 99% CI, -21.1 to -2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30).
Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.
在 PD-L1 肿瘤细胞阳性表达率（TC）≥25%的转移性非小细胞肺癌（NSCLC）患者中，度伐利尤单抗联合或不联合 Tremelimumab 对比化疗的 3 期 MYSTIC 研究未达到主要终点。我们报告了患者报告的结局（PRO）。
未经治疗的患者按 1:1:1 的比例随机分为度伐利尤单抗组、度伐利尤单抗+ Tremelimumab 组或化疗组。采用 EORTC 生活质量问卷（QLQ）-C30/LC13 对 PD-L1 TC≥25%的患者进行 PRO 评估。采用重复测量混合模型（MMRM）分析预设 PRO 终点的变化，采用分层对数秩检验分析至恶化时间（TTD）。
488 例患者中，各组间基线 PRO 无差异。与化疗组相比，至少一种度伐利尤单抗组的 MMRM 调整后的平均基线变化差异具有统计学意义（名义 P<0.01）：C30 疲劳：度伐利尤单抗（-9.5；99%置信区间[CI]，-17.0 至-2.0），度伐利尤单抗+ Tremelimumab（-11.7；99%CI，-19.4 至-4.1）；C30 食欲丧失：度伐利尤单抗（-11.9；99%CI，-21.1 至-2.7）。与化疗组相比，至少一种度伐利尤单抗组的 TTD 更长（名义 P<0.01）：全球健康状况/生活质量：度伐利尤单抗（HR=0.7；95%CI，0.5-1.0），度伐利尤单抗+ Tremelimumab（HR=0.7；95%CI，0.5-1.0）；体力状况：度伐利尤单抗（HR=0.6；95%CI，0.4-0.8），度伐利尤单抗+ Tremelimumab（HR=0.6；95%CI，0.5-0.9）（均为 C30）；呼吸困难等关键症状：度伐利尤单抗（HR=0.6；95%CI，0.5-0.9），度伐利尤单抗+ Tremelimumab（HR=0.7；95%CI，0.5-1.0）（均为 LC13）；疲劳：度伐利尤单抗+ Tremelimumab（HR=0.6；95%CI，0.4-0.8）；食欲丧失：度伐利尤单抗（HR=0.5；95%CI，0.4-0.7），度伐利尤单抗+ Tremelimumab（HR=0.7；95%CI，0.5-0.9）（均为 C30）。
与化疗相比，度伐利尤单抗± Tremelimumab 降低了症状负担，改善了转移性 NSCLC 患者的 PRO 生存质量和 TTD，表明其对患者的生活质量无不利影响。
