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2015年ASCO年会于5月29日—6月2日在美国芝加哥召开。5月30日下午消化系统（结直肠）肿瘤口头报告专场上，一项摘要号为3502的SIRFLOX研究，在在转移性结直肠癌（mCRC）患者中将一线mFOLFOX6±贝伐珠单抗（bev）与mFOLFOX6＋选择性体内放射疗法（SIRT）±bev进行比较。医脉通整理如下：

SIRFLOX研究旨在评估应用钇-90（yttrium-90，Y-90）的FOLFOX化疗（±bev）联合SIRT作为mCRC肝转移患者一线治疗的疗效和安全性。

研究方法：

SIRFLOX是一项在化疗-初治的不可切除，仅肝或肝占位（肝联合肺和/或淋巴结转移）mCRC患者中的国际性，多中心，开放标签，随机对照试验。A组：mFOLFOX6±bev与B组：mFOLFOX6+SIRT（SIR-Spheres；Sirtex）第一个周期给药1次±bev进行比较，直至疾病进展。主要终点是应用RECIST v1.0标准的无进展生存期（PFS）。分层变量包括额外的肝脏疾病存在（EHD；只有肝 v 肝占位），肝脏受累程度（≤25% v ＞25%），联合bev治疗（由临床医生判断）。

研究结果：

从2006年10月到2014年4月，有530例患者随机分配入组（A组，n=263；B组，n=267），212例（40%）患者有EHD。中位随访时间是36.1个月。按照Kaplan Meier分析中位总PFS在A组 v B组是10.2个月 v 10.7个月（风险比[HR]：0.93；95% CI 0.77～1.12；P=0.428）。根据竞争性风险分析肝脏病变的中位PFS在A组 v B组是12.6个月 v 20.5个月（HR：0.69；95% CI 0.55～0.90；P=0.002）。A组 v B组的总缓解率（PR+CR）分别为68.0% v 76.4%（P=0.113）。肝缓解率是68.8% v 78.7%（P=0.042），包括CR率1.9% v 6.0%（P=0.02）。肝脏切除率在A组 v B组为13.7% v 14.2%（P=0.857）。注意的是，≥3级不良事件在A组 v B组是73.3% v 85.4%。最常见的毒性反应是血液问题，32.9% v 51.2%；胃肠道问题，21.2% v 32.9%，包括胃溃疡0.0% v2.4%。

结论：

在不-可切除CRC肝转移患者的一线治疗中，将SIRT增加到标准化疗未能改善整体PFS。然而，中位肝脏PFS显著延长。SIRT的增加与可接受的毒性反应相关。结合来自SIRFLOX和另两项该疾病研究的数据对总生存期分析正在进行中。临床试验信息：NCT00724503。

会议专题》》》2015年ASCO年会专题报道

阅读摘要原文

SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bev in patients (pts) with metastatic colorectal cancer (mCRC).（Abstract 3502）

Authors：‍‍ Peter Gibbs, Volker Heinemann‍‍,et al.

Session Type：Oral Abstract Session

Background：The SIRFLOX study was designed to assess the efficacy and safety of combining FOLFOX chemotherapy (± bev) with SIRT using yttrium-90 (Y-90) resin microspheres as first-line treatment of pts with liver metastases from mCRC. 

Methods：SIRFLOX was an international, multi-center, open-label, RCT in chemotherapy-naïve pts with non-resectable, liver only or liver dominant (liver plus lung and/or lymph node metastases) mCRC. Arm A: mFOLFOX6 ± bev was compared to arm B: mFOLFOX6 + SIRT (SIR-Spheres; Sirtex) administered once with cycle 1 ± bev until disease progression. The primary endpoint was progression free survival (PFS) using RECIST v1.0. Stratification variables included presence of extra hepatic disease (EHD; liver only v liver dominant), degree of liver involvement ( ≤ 25% v > 25%), and treatment with bev (at clinician discretion). 

Results：From Oct 2006 to Apr 2013,530 pts were randomised (arm A, n = 263; arm B, n = 267), 212 (40%) had EHD. Median follow-up was 36.1 months. The median overall PFS was 10.2 v 10.7 months in arms A v B respectively (hazard ratio [HR]: 0.93; 95% CI 0.77–1.12; p=0.428) by Kaplan Meier analysis. The median PFS in the liver was 12.6 v 20.5 months in arm A v B (HR: 0.69; 95% CI 0.55–0.90; p = 0.002) by competing risk analysis. Overall response rate (PR + CR) was 68.0% v 76.4% in arm A v B, respectively (p = 0.113). Hepatic response rate was 68.8% v 78.7% in arm A v B (p = 0.042), including CR rate 1.9% v 6.0% (p = 0.02). The liver resection rate was 13.7% v 14.2% in arm A v B (p = 0.857). Adverse events ≥ grade 3 were noted in 73.3% v 85.4% of pts in arm A v B. Most common toxicities were hematologic; 32.9% v 51.2% and gastrointestinal; 21.2% v 32.9%, including gastric ulcer 0.0% v2.4%. 

Conclusion：In first-line treatment of pts with non-resectable CRC liver metastases, the addition of SIRT to standard chemotherapy failed to improve overall PFS. However, median liver PFS was significantly extended. The addition of SIRT was associated with acceptable toxicity. Overall survival analyses, combining data from SIRFLOX and two other ongoing studies in this disease setting, are awaited. Clinical trial information: NCT00724503