2014年ESMO大会于9月26日-30日在西班牙马德里召开。会上公布的一项Q2试验旨在评估在卡培他滨（CAP）单药治疗方案中增加贝伐单抗是否可以延长原发肿瘤切除后的结直肠癌患者的无病生存期和总生存期，从而验证假设，找出贝伐单抗疗效和毒性的新的标志物。
研究方法
这一国际性的III期随机对照试验是在英国和其他6国进行的。除了收集毒性作用、无病生存期和总生存期的数据以外，还建立了包括1350个福尔马林固定石蜡包埋的标本和1000个种系DNA的生物样本库。我们对假设驱动的生物标志物(MSI状态和上皮/基质比)和假设驱动的生物标志物(染色体不稳定型,ras, raf, POLE和80基因的离子流panel)进行了分析来评价它们的预测和预后作用。
研究结果
根据人口统计学特点和疾病的特点进行分层后，将1941位患者按1:1的比例随机分配到两个组中。整个实验人群中的无病生存期表明，贝伐单抗不会提高疗效(CAP+贝伐单抗治疗组患者的3 年无病生存率 75.2%，而CAP单药治疗组患者的3年无病生存率78.2%； HR = 1.06; p = 0.54)。与之相似，总生存期也未提高(CAP+贝伐单抗治疗组患者的3 年总生存率为85.5%，而CAP单药治疗组患者的3年总生存率87.2%; p = 0.38; HR = 1.12)。HR可能有时间趋势(HRs: 1年 0.83[0.61-1.13], 2年 0.87[0.65-1.17],3年 1.32 [0.9-1.98]。生物标志物分析确认，肿瘤基质多提示疾病预后差(3 年无病生存率 HR 1.58 [1.22-2.05]; p = 0.001)。与CAP单药治疗的患者相比，应用CAP/贝伐单抗治疗的患者MSS阳性提示患者的无病生存期更短(n = 840; HR 1.43; p = 0.005)。这提示贝伐单抗的阴性预测结果：MSI阳性的患者中，两组患者的无病生存期没有明显差别。
结论
Q2试验支持其他两个试验的数据，提示贝伐单抗在结直肠癌的辅助治疗中不起作用。Q2生物样本库和联网的数据库支持做进一步合作的生物标志物假说的检测。我们可以对所有贝伐单抗辅助治疗结直肠癌的研究进行荟萃分析，从而更加充分的探索贝伐单抗对无进展生存期的时间效应。
英文原文
FINAL RESULTS FROM QUASAR2, A MULTICENTRE,INTERNATIONAL RANDOMISED PHASE III TRIALOF CAPECITABINE (CAP) +/- BEVACIZUMAB (BEV) IN THE ADJUVANT SETTING OF STAGE II/III COLORECTAL CANCER (CRC)（摘要号：LBA12）
Aim: The aims of Q2 were to assess whether the addition of BEV 7.5mg/kg q3/52 (12/ 12) to single agent CAP 1250mg/m2 , 14 of every 21/7 (6/12), increases disease-free (DFS) and overall survival (OS) in CRC patients after resection of the primary; and to validate suggested, or discover new, biomarkers of BEV efficacy and toxicity.
Methods: A phase III international randomised controlled trial, coordinated by the UK and recruiting in 6 countries. In addition to the collection of data on toxicity, DFS and OS, a biobank comprising 1350 FFPE blocks and 1000 germline DNA samples was established. Hypothesis-driven biomarkers (MSI status and epithelial/stromal ratio) and hypothesis-driven biomarkers (chomosomal instabiity, ras, raf, POLE and an 80-gene ion torrent panel) were analysed to assess their prognostic and predictive (BEV) utility.
Results: 1941 patients were randomised in a 1:1 ratio and demographics and disease characteristics were well balanced between the two arms. DFS in the whole trial population demonstrates that BEV does not improve outcome in this setting (3 year DFS 75.2% for CAPBEV vs 78.2% for CAP: HR = 1.06; p = 0.54). Similarly OS was not improved (3 year OS 85.5% for CAPBEV vs 87.2% for CAP; p = 0.38; HR = 1.12). There may be a temporal trend in HRs (HRs: 1 year 0.83[0.61-1.13], 2 year 0.87[0.65-1.17],3 year 1.32 [0.9-1.98]. Biomarker analyses confirm that high tumour stromal content confers a worse prognosis (3 year DFS HR 1.58 [1.22-2.05]; p = 0.001). MSS positivity was associated with a worse DFS in patients treated with CAP/BEV compared to those treated with CAP alone (n = 840; HR 1.43; p = 0.005) suggesting a negative predictive effect for BEV: For MSI positive patients, there was no significant difference in DFS between the two arms (n = 135; HR 0.74; p = 0.42).
Conclusions: Q2 supports data from two other trials suggesting no role for BEV in the adjuvant setting of CRC. The Q2 biobank and linked database allows further collaborative biomarker hypotheses to be tested. There is a rationale for meta-analysis of all BEV adjuvant CRC studies to more fully explore the putative temporal effect of BEV administration on DFS.
会议专题》》》2014年ESMO大会专题报道
