医脉通编译，转载请务必注明出处

2015年ASCO年会于5月29日—6月2日在美国芝加哥召开。5月31日上午的消化系统（非结直肠）肿瘤口头报告专场上，摘要号为4005的一项随机II期研究，在局部晚期或转移性胰腺神经内分泌瘤（pNET）患者中，将依维莫司（E）与依维莫司+贝伐珠单抗（E+B）进行了比较评估。医脉通整理如下：

VEGF通路和mTOR两种抑制剂在胰腺神经内分泌瘤是有活性的。经mTOR抑制剂依维莫司（E）的治疗会改善无进展生存期（PFS），但是如果一种VEGF通路抑制剂中加入一种mTOR抑制剂是否增强pNET中抗肿瘤活性是未知的。这项随机II期研究将依维莫司或依维莫司+贝伐珠单抗治疗晚期pNET患者进行了评估。

研究方法：

患者按照1:1随机分配接受E（10mg po qd）或E（10mg po qd）联合B（10mg/kg IV q 2 wks）给药。这两组患者同期接受标准剂量奥曲肽。主要终点是PFS。应用90%区间的分层log-rank检验（单侧α=0.15）评估E+B vs E的潜在优势。次要终点包括总生存期（OS），缓解率（RR），和安全性。

研究结果：

150例患者随机分配，每组75人。治疗组之间的患者特征相似，包括：中位年龄59岁（范围21～86），56%的男性，ECOG评分为0（57%）和1（43%），24%的患者之前接受细胞毒性化疗。中位28天治疗周期是13天（E+B）和12天（E），有1～44个周期的范围。中位随访期是25.9个月。

接受E+B的患者出现3级AEs的频率较高，包括腹泻（14% vs 3%；P=0.01），低钠血症（12% vs 3%；P=0.02），低磷血症（11% vs 3%；P= 0.04），蛋白尿（16% vs 1%；P=0.001），和高血压（41% vs 12%；P＜0.0001）。在两组中4级AEs的发生率是11%；单独的5级事件发生在E组。

中位PFS是16.7个月（E+B） vs 14个月（E）；HR=0.80（95% CI：0.55～1.17；116例PFS事件），单侧P=0.12。中位OS是36.7个月（E+B） vs 35个月（E）；HR=0.75（95% CI：0.42～1.13；49例OS事件），单侧P=0.16。与单独的E治疗（12%）相比较，E+B治疗有显著较高的RR（31%），P=0.005。

结论：

在这项随机II期研究中，与依维莫司相比较，依维莫司+贝伐珠单抗的治疗会带来有优势的无进展生存期，但是会伴有较多的不良事件。经依维莫司+贝伐珠单抗治疗患者的PP显著较高。依维莫司+贝伐珠单抗联合方案在晚期pNET患者中需要进一步的研究。临床试验信息：NCT01229943。

会议专题》》》2015年ASCO年会专题报道

阅读摘要原文：

Randomized phase II study of everolimus (E) versus everolimus plus bevacizumab (E+B) in patients (Pts) with locally advanced or metastatic pancreatic neuroendocrine tumors (pNET), CALGB 80701 (Alliance).

Authors：Matthew H. Kulke, Donna Niedzwiecki‍,‍‍et al.

Session Type：Oral Abstract Session

Background：Both VEGF pathway and mTOR inhibitors are active in pNET. Treatment with the mTOR inhibitor E improves progression free survival (PFS), but it is not known if the addition of a VEGF pathway inhibitor to an mTOR inhibitor enhances antitumor activity in pNET. This randomized phase II study evaluated E or E+B in pts with advanced pNET. 

Methods：Pts were randomized 1:1 to receive either E (10 mg po qd) or E (10 mg po qd) co-administered with B (10 mg/kg IV q 2 wks). Pts in both arms received concurrent standard dose octreotide. The primary endpoint was PFS. The potential superiority of E+B vs. E was assessed using a stratified log-rank test with 90% power (1-sided α = 0.15) to detect a HR of 0.64. Secondary endpoints included overall survival (OS), response rate (RR), and safety. 

Results：150 pts were randomized; 75 per arm. Pt characteristics were similar between treatment arms and included: median age 59 years (range 21-86), 56% male, ECOG PS 0 (57%) and 1 (43%), prior cytotoxic chemotherapy 24%. The median number of 28-day treatment cycles was 13 (E+B) and 12 (E), with a range of 1-44 cycles. Median follow up was 25.9 months. Pts on E+B experienced a higher frequency of grade 3 AEs, including diarrhea (14% vs. 3%; p = 0.01), hyponatremia (12% vs. 3%; p = 0.02), hypophosphatemia (11% vs. 3%; p = 0.04), proteinuria (16% vs. 1%; p = 0.001), and hypertension (41% vs. 12%; p < 0.0001). The frequency of grade 4 AEs was 11% in both arms; a single grade 5 event occurred on E. The median PFS was 16.7 mos (E+B) vs. 14 mos (E); HR = 0.80 (95% CI: 0.55, 1.17; 116 PFS events), 1-sided p = 0.12. The median OS was 36.7 mos (E+B) vs. 35.0 mos (E), HR = 0.75 (95% CI: 0.42-1.33; 49 OS events), 1-sided p = 0.16. Treatment with E+B was associated with a significantly higher RR (31%) compared to E alone (12%), p = 0.005) .

Conclusions：Treatment with E+B led to superior PFS compared to E but with more adverse events in this randomized phase II study. The RR was significantly higher in pts treated with E+B. The combination of E+B warrants further investigation in pts with advanced pNET. Clinical trial information: NCT01229943