Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, IL.
Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2021 Dec 10;39(35):3897-3907. doi: 10.1200/JCO.21.01839. Epub 2021 Sep 20.
To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).
In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and mutation status.
Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% 49.3%). Both groups received full chemotherapy dose intensity.
The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.
研究经动脉钇-90 放射性栓塞术（TARE）联合二线系统化疗治疗结直肠癌肝转移（CLM）的效果。
在这项国际性、多中心、开放性 III 期临床试验中，接受奥沙利铂或伊立替康为基础的一线治疗后进展的 CLM 患者被随机 1:1 分配接受二线化疗加或不加 TARE。两个主要终点是无进展生存期（PFS）和肝脏无进展生存期（hPFS），通过盲法独立中心评估。随机分组采用基于单叶或双叶疾病、奥沙利铂或伊立替康为基础的一线化疗以及 突变状态的基于网络或语音的系统进行分层。
来自北美、欧洲和亚洲 95 个中心的 428 名患者被随机分配至化疗加或不加 TARE 治疗；这是意向治疗人群，包括 TARE 加化疗组 215 名患者和单独化疗组 213 名患者。PFS 的风险比（HR）为 0.69（95%CI，0.54 至 0.88；单侧 =.0013），中位 PFS 分别为 8.0（95%CI，7.2 至 9.2）和 7.2（95%CI，5.7 至 7.6）个月。hPFS 的 HR 为 0.59（95%CI，0.46 至 0.77；单侧 <.0001），中位 hPFS 分别为 9.1（95%CI，7.8 至 9.7）和 7.2（95%CI，5.7 至 7.6）个月。TARE 和化疗组的客观缓解率分别为 34.0%（95%CI，28.0 至 40.5）和 21.1%（95%CI，16.2 至 27.1；单侧 =.0019）。TARE 和化疗组的中位总生存期分别为 14.0（95%CI，11.8 至 15.5）和 14.4 个月（95%CI，12.8 至 16.4；单侧 =.7229），TARE 和化疗组的 HR 分别为 1.07（95%CI，0.86 至 1.32）。TARE 组更常报告 3 级不良事件（68.4% 49.3%）。两组均接受了全剂量化疗强度。
二线 CLM 患者接受 TARE 联合系统治疗可延长 PFS 和 hPFS。需要进一步的亚组分析来更好地确定从 TARE 中获益的理想患者人群。
