PURPOSE To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. METHODS In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. RESULTS Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. CONCLUSIONS 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11.

中文翻译：

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肝脏肿瘤负荷、碱性磷酸酶升高和靶病变大小对 177Lu-Dotatate 治疗结果的影响：NETTER-1 研究分析。

目的 评估基线肝肿瘤负荷、碱性磷酸酶 (ALP) 升高和靶病变大小对 177Lu-Dotatate 治疗结果的影响。方法 在 3 期 NETTER-1 试验中，晚期进展性中肠神经内分泌肿瘤 (NET) 患者被随机分配至 177Lu-Dotatate（每 8 周，四个周期）加奥曲肽长效释放剂 (LAR) 或奥曲肽 LAR 60 mg . 主要终点是无进展生存期（PFS）。使用 Kaplan-Meier 估计按基线因素分析 PFS，包括肝肿瘤负荷、ALP 升高和靶病变大小；使用 Cox 回归估计具有相应 95% CI 的风险比 (HR)。结果 在低 (< 25%)、中 (25-50%)、和高 (> 50%) 肝肿瘤负荷 (HR 0.187, 0.216, 0.145)，ALP 正常或升高 (HR 0.153, 0.177)，以及存在或不存在大靶病变（直径 > 30 mm；HR， 0.213，0.063）。在 177Lu-Dotatate 组中，在低/中/高肝肿瘤负荷 (P = 0.7225) 或基线 ALP 正常/升高 (P = 0.3532) 但没有大靶病变的患者中，未观察到 PFS 的显着差异与改善的 PFS 相关（P = 0.0222）。3 级和 4 级肝功能异常很少见，似乎与高基线肝肿瘤负荷无关。结论 177Lu-Dotatate 在晚期进展性中肠 NET 患者中与大剂量奥曲肽 LAR 相比，PFS 显着延长，无论基线肝肿瘤负荷如何、ALP 升高、或存在大的靶病变。Clinicaltrials.gov：NCT01578239，EudraCT：2011-005049-11。