CheckMate 649研究中一线纳武利尤单抗联合化疗与单纯化疗用于晚期胃癌、胃食管交界癌或食管腺癌患者的Q-TWiST分析：4年随访结果
Q-TWiST analysis of first-line nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma from CheckMate 649: 4-year follow-up results.
作者信息
Lin Daniel, Quan Wenying, Garretson Marne, Chirikov Viktor, Chen Clara, Singh Prianka, Davis Catherine, Sugarman Ryan
机构信息
Department of Medical Oncology, Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 700 College Building, Philadelphia, PA, 19107, USA.
OPEN Health, HEOR and Market Access, 1140 6 Ave., Floor 18, New York, NY, 10036, USA.
出版信息
Gastric Cancer. 2025 Jul 9. doi: 10.1007/s10120-025-01634-6.
BACKGROUND
Nivolumab plus chemotherapy demonstrated clinically significant improvement in quality-adjusted survival versus chemotherapy alone as first-line treatment for advanced non-HER2-positive gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC) in the CheckMate 649 post-hoc quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis at 1-year minimum follow-up. We report Q-TWiST analysis results at 4-year minimum follow-up.
METHODS
Q-TWiST methodology was applied post-hoc to CheckMate 649 study data from all randomized patients, patients with PD-L1 combined positive score (CPS) ≥ 1, and patients with PD-L1 CPS ≥ 5. Relative Q-TWiST gains ≥ 10% were predefined as clinically important and ≥ 15% as clearly clinically important.
RESULTS
Among all randomized patients, patients with PD-L1 CPS ≥ 1, and patients with PD-L1 CPS ≥ 5, mean (95% CI) absolute Q-TWiST gains of 3.4 (1.8-5.1), 4.2 (2.4-6.1), and 5.4 (3.0-7.7) months with nivolumab plus chemotherapy versus chemotherapy were observed, respectively. These translated to clearly clinically important relative Q-TWiST gains of 20.5%, 26.1%, and 33.4% in each population; relative Q-TWiST gains benefit remained clearly clinically important in all subgroups (15.7%, 20.3%, and 26.4%) after expanding the analysis to include grade 2 adverse events. Greater Q-TWiST gains were observed with nivolumab plus chemotherapy across most subgroups in all randomized patients and patients with PD-L1 CPS ≥ 1 and across all subgroups in patients with PD-L1 CPS ≥ 5.
CONCLUSION
Clearly clinically important benefit in quality-adjusted survival with first-line nivolumab plus chemotherapy versus chemotherapy was observed across all evaluated PD-L1 CPS expression levels in patients with advanced GC/GEJC/EAC from CheckMate 649 with 4-year minimum follow-up.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT02872116.
背景
在CheckMate 649事后质量调整无症状或毒性时间（Q-TWiST）分析中，纳武利尤单抗联合化疗作为晚期非HER2阳性胃癌、胃食管交界癌和食管腺癌（GC/GEJC/EAC）的一线治疗，与单纯化疗相比，在质量调整生存方面显示出具有临床意义的改善，该分析的最短随访时间为1年。我们报告了最短随访时间为4年的Q-TWiST分析结果。
方法
将Q-TWiST方法事后应用于CheckMate 649研究中所有随机分组患者、程序性死亡受体配体1（PD-L1）联合阳性评分（CPS）≥1的患者以及PD-L1 CPS≥5的患者的数据。相对Q-TWiST增益≥10%被预先定义为具有临床重要性，≥15%被定义为明显具有临床重要性。
结果
在所有随机分组患者、PD-L1 CPS≥1的患者以及PD-L1 CPS≥5的患者中，与化疗相比，纳武利尤单抗联合化疗的平均（95%CI）绝对Q-TWiST增益分别为3.4（1.8-5.1）、4.2（2.4-6.1）和5.4（3.0-7.7）个月。这在各人群中转化为明显具有临床重要性的相对Q-TWiST增益，分别为20.5%、26.1%和33.4%；在将分析扩大至包括2级不良事件后，所有亚组中的相对Q-TWiST增益益处仍明显具有临床重要性（15.7%、20.3%和26.4%）。在所有随机分组患者和PD-L1 CPS≥1的患者中的大多数亚组以及PD-L1 CPS≥5的患者的所有亚组中，纳武利尤单抗联合化疗均观察到更大的Q-TWiST增益。
结论
在CheckMate 649研究中，对晚期GC/GEJC/EAC患者进行了最短随访时间为4年的评估，结果显示，在所有评估的PD-L1 CPS表达水平上，一线纳武利尤单抗联合化疗与化疗相比，在质量调整生存方面具有明显的临床重要益处。
试验注册
ClinicalTrials.gov标识符，NCT02872116。
Zotero 插件