背景:评估经一线化疗(EPOCH)进展的转移性肝癌患者的经动脉放射栓塞(TARE)显示,使用钇90玻璃微球联合化疗(TARE/Chemo)治疗结直肠癌肝转移的效果优于化疗(Chemo)。进行了额外的探索性分析,以评估TARE/Chemo对疗效的影响,安全,后续治疗的时间,生活质量恶化的时间(QoL),并确定改善患者选择的标准。
方法:分析了主要研究人群的QoL恶化时间。随后,进行了事后分析,以确定TARE/Chemo与Chemo改善了QoL恶化时间的亚组.无进展生存期(PFS),肝(h)PFS,后续治疗的时间,比较了两种治疗方法的安全性结局.
结果:主要人群在治疗组之间的QoL恶化时间上没有显着差异;但是,在2个已确定的亚组中观察到显著性,即:A亚组(N=303)排除了两个治疗组的东部肿瘤协作组(ECOG)1和基线CEA≥35ng/mL患者;B亚组(N=168)还排除了KRAS(Kirsten大鼠肉瘤)突变患者.在亚组A中,TARE/Chemo患者(N=143)与Chemo(N=160)相比表现出更好的结局:PFS(9.4vs.7.6个月,危险比(HR):0.64;单侧P=.0020),hPFS(10.8vs.7.6个月,HR:0.53;单侧P<.0001),QoL恶化的时间(5.7与3.9个月,HR:0.65;单侧P=.0063),和后续治疗的时间(21.2vs.10.5个月,HR:0.52;单侧P<0.0001)。B亚组患者在治疗组之间显示出相似但更大的显着差异。PFS中位数,hPFS,TARE/Chemo在两个亚组中与主要人群相比,QoL恶化的时间在数字上更长,B亚组差异最大,TARE/Chemo与单独化疗相比,两个亚组的CEA应答者百分比更高,ORR改善。在所有人群中,化疗的安全性(报告为事件发生率/100患者-年)更高。还报告了在主要人群中的其他功效分析。
结论:谨慎选择患者,包括考虑预后因素ECOG,基线CEA,和KRAS状态,设定适合TARE/Chemo作为二线治疗的结直肠癌肝转移患者的结局预期(试验登记号:NCT01483027)。
BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection.
METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments.
RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N = 143) demonstrated superior outcomes vs Chemo (N = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported.
CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).