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在美国旧金山举行的2016年胃肠道肿瘤论坛会上，研究者报告了一项开始于胃肠道或起源不明的神经内分泌肿瘤患者的III期研究RADIANT-4。研究结果显示，与安慰剂相比，依维莫司与癌症恶化前6-8个月的延长期相关（摘要号315）。
ASCO观点
“尽管依维莫司已经被批准用于胰腺神经内分泌肿瘤的治疗，但这些结果表明，依维莫司可能对更广泛的神经内分泌肿瘤患者有效”，“这项研究为接受其它治疗后肿瘤恶化的患者提供了新的治疗选择”。
——ASCO发言人Smitha Krishnamurthi
研究详情
主要研究作者多伦多Sunnybrook’s 奥德特癌症中心的医学肿瘤学家Simron Singh 说道：“依维莫司有可能在更长的一段时间内防止癌症发展。”
该分析纳入了175位经治的、晚期GI神经内分泌肿瘤患者。其中36位具有起源部位不明的神经内分泌肿瘤。所有的患者为非功能性肿瘤，即起初肿瘤很少或不引发症状。
Dr. Singh 表示：“在咨询肿瘤科医生的过程中，神经内分泌肿瘤患者可能把这项治疗看成是新的标准治疗选择之一。”
研究人员将患者随机分配接受依维莫司加最佳支持治疗，或安慰剂加最佳支持治疗。所有患者的肿瘤在其它治疗过程中均发生了进展，包括生长抑素类似物（神经内分泌肿瘤的一种标准激素治疗），手术或化疗。
总之，与安慰剂相比，依维莫司减少了40%的疾病进展风险。在GI神经内分泌肿瘤患者中，依维莫司组的中位无进展生存为13.1个月，安慰剂组为5.4个月。在起源不明组，依维莫司组肿瘤患者的中位无进展生存为13.6个月，安慰剂组为7.5个月。
依维莫司组的最常见的不良反应事件是口腔炎（口腔炎症），感染，腹泻，外周性水肿和疲劳。神经内分泌肿瘤是一组开始于身体多种器官内产生激素（神经内分泌）的细胞的癌症。大多数神经内分泌肿瘤开始于胃肠道。尽管这种疾病并不常见（在美国每年仅仅有8000人确诊为胃肠道神经内分泌肿瘤），然而神经内分泌肿瘤的发生率却在增加。
Dr. Singh 表示：“目前，GI神经内分泌肿瘤患者只有有限的治疗选择，因此这项研究在该流域非常受欢迎，打开了一扇通往新型治疗的大门”。依维莫司之前已经被批准用于胰腺神经内分泌肿瘤治疗。
摘要原文
Abstract 315: Efficacy and safety of everolimus in advanced, progressive, nonfunctional neuroendocrine tumors (NET) of the gastrointestinal (GI) tract and unknown primary: A subgroup analysis of the phase III RADIANT-4 trial.
Background: In the groundbreaking, phase 3 RCT RADIANT-4 study, everolimus (EVE) significantly prolonged median progression-free survival (PFS) by 7.1 mo in patients (pts) with advanced, progressive, nonfunctional NET of GI or lung vs placebo (PBO); HR, 0.48 (95%CI, 0.35-0.67), P<0.00001 [Yao JC et al, ECC-ESMO, 2015].
Methods: In RADIANT-4, pts with advanced, progressive, well-differentiated (G1/G2), nonfunctional GI or lung NET were randomized (2:1) to EVE (10 mg/d) or PBO. In this analysis, pts with NET of GI tract (stomach, colon, rectum, appendix, caecum, ileum, duodenum, jejunum, or small intestine) and unknown primary were included.
Results: Of 302 pts, 175 had GI NET (EVE [n=118], PBO [n=57]); 36 had NET of unknown primary (EVE [23], PBO [13]). In GI NET pts, median age was 63 y; females: 55%; G1/G2: 75%/25%; WHO PS: 0, 78% or 1, 22%; Caucasian: 73%. Similar baseline characteristics were observed in pts with NET of unknown primary. Ileum (41%), rectum (23%) and jejunum (13%) were the most common locations in GI subgroup. The table below lists prior treatments. In pts with GI NET, median PFS (95% CI) by central review (EVE vs PBO) was 13.1 (9.2-17.3) mo vs 5.4 (3.6-9.3) mo with an estimated 44% risk-reduction in favor of EVE (HR, 0.56; 95% CI, 0.37-0.84). In pts with NET of unknown primary, median PFS (95% CI) by central review (EVE vs PBO) was 13.6 (4.1-not evaluable) mo vs 7.5 (1.9-18.5) mo (HR, 0.60; 95% CI, 0.24-1.51). The most frequent G3/4 adverse events irrespective of drug-relationship reported in ≥5% pts in GI subgroup were diarrhea, hypertension, stomatitis, abdominal pain, fatigue, and acute renal failure.
Conclusions: The present subgroup analysis of RADIANT-4 study demonstrated improvement in PFS with EVE for pts with GI NET, and suggests efficacy in NET of unknown primary, with an estimated 40% to 44% risk-reduction in favor of EVE vs PBO. Safety profile for EVE is consistent with that previously reported.
医脉通编译自：www.asco.org/gipresskit • www.gicasym.org
