Yao James C, Guthrie Katherine A, Moran Cesar, Strosberg Jonathan R, Kulke Matthew H, Chan Jennifer A, LoConte Noelle, McWilliams Robert R, Wolin Edward M, Mattar Bassam, McDonough Shannon, Chen Helen, Blanke Charles D, Hochster Howard S
James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
J Clin Oncol. 2017 May 20;35(15):1695-1703. doi: 10.1200/JCO.2016.70.4072. Epub 2017 Apr 6.
Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.
目的 神经内分泌肿瘤（NETs）的治疗选择仍然有限。本试验评估了在晚期NETs患者中，贝伐单抗或干扰素α-2b（IFN-α-2b）联合奥曲肽治疗的无进展生存期（PFS）。
患者与方法 西南肿瘤协作组（SWOG）S0518是一项在美国协作组系统中开展的III期研究，纳入了患有进展性疾病或其他预后不良特征的1级和2级晚期NETs患者。患者被随机分配接受每21天一次20mg长效奥曲肽治疗，同时每21天接受一次15mg/kg贝伐单抗治疗，或每周三次500万单位IFN-α-2b治疗。主要终点为中心评估的PFS。本试验已在ClinicalTrials.gov注册，注册号为NCT00569127。
结果 共入组427例患者，其中214例被分配至贝伐单抗组，213例被分配至IFN-α-2b组。中心评估的贝伐单抗组中位PFS为16.6个月（95%CI，12.9至19.6个月），IFN组为15.4个月（95%CI，9.6至18.6个月）（风险比[HR]，0.93；95%CI，0.73至1.18；P = 0.55）。经研究现场评估，贝伐单抗组中位PFS时间为15.4个月（95%CI，12.6至17.2个月），干扰素组为10.6个月（95%CI，8.5至14.4个月）（HR，0.90；95%CI，0.72至1.12；P = 0.33）。贝伐单抗组至治疗失败时间长于IFN组（HR，0.72；95%CI，0.58至0.89；P = 0.003）。确认的影像学缓解率贝伐单抗组为12%（95%CI，8%至18%），IFN组为4%（95%CI，2%至8%）。贝伐单抗与奥曲肽联合治疗的常见不良事件包括高血压（32%）、蛋白尿（9%）和疲劳（7%）；IFN与奥曲肽联合治疗的不良事件包括疲劳（27%）、中性粒细胞减少（12%）和恶心（6%）。
结论 贝伐单抗组和IFN组在PFS方面未观察到显著差异，这表明这些药物在晚期NETs患者中具有相似的抗肿瘤活性。
