¹⁷⁷Lu-DOTATATE has emerged as a viable treatment strategy for advanced well-differentiated grade 1/2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Few retrospective studies have shown concomitant ¹⁷⁷Lu-DOTATATE with radiosensitizing low-dose capecitabine to be effective in advanced NETs. However, this has not been validated in prospective randomized-controlled trials. Methods: In this investigator-initiated, parallel-group, open-label, phase 2 trial, patients with grade 1/2 GEP-NETs, having progressive somatostatin receptor–positive, locally advanced, or metastatic disease on ⁶⁸Ga-DOTANOC PET/CT, were randomly assigned in a 1:1 ratio to ¹⁷⁷Lu-DOTATATE plus capecitabine (experimental arm) or ¹⁷⁷Lu-DOTATATE only (control arm). ¹⁷⁷Lu-DOTATATE was administered at approximately 7.4 GBq/cycle intravenously, for up to 4 cycles, at 8 wk intervals, whereas capecitabine was given at 1,250 mg/m²/d orally from day 0 to day 14 of each cycle of ¹⁷⁷Lu-DOTATATE. The primary endpoint was the objective response rate. Secondary endpoints included the disease control rate, progression-free survival, overall survival, and adverse events. Results: Seventy-two patients (median age, 53 y; range, 18–79 y) were enrolled. The objective response rate was 33.3% (95% CI, 18.6–50.9%) in the experimental arm versus 30.6% (95% CI, 16.4–48.1%) in the control arm (P = 0.800). The disease control rate was 88.9% (95% CI, 73.9–96.9%) and 91.7% (95% CI, 77.5–98.2%) in the experimental and control arms, respectively (P = 1.000). The estimated median progression-free survival in the experimental arm was 29 mo (95% CI, 22–29 mo) versus 31 mo (95% CI, 29–32 mo) in the control arm (P = 0.401). The median overall survival was not reached in either arm (P = 0.876). Overall, adverse events of at least grade 3 were noted in 7 patients in the experimental arm versus 6 patients in the control arm (P = 0.759). Conclusion: Based on the results of this trial, the addition of low-dose capecitabine to ¹⁷⁷Lu-DOTATATE in advanced grade 1/2 GEP-NETs did not lead to superior radiographic responses. Further studies are needed to evaluate its potential role in high-grade NETs.

¹⁷⁷ 元Lu-DOTATATE 已成为晚期高分化 1/2 级胃肠胰神经内分泌瘤 （GEP-NET） 的可行治疗策略。很少有回顾性研究表明，¹⁷⁷Lu-DOTATATE 与放射增敏低剂量卡培他滨联合治疗晚期 NET 有效。然而，这尚未在前瞻性随机对照试验中得到验证。方法：在这项由研究者发起的平行组开放标签 2 期试验中，1/2 级 GEP-NETs 患者，在 ⁶⁸Ga-DOTANOC PET/CT 上出现进行性生长抑素受体阳性、局部晚期或转移性疾病，以 1：1 的比例随机分配到 ¹⁷⁷Lu-DOTATATE 加卡培他滨组（实验组）或仅 ¹⁷⁷Lu-DOTATATE（对照组）。¹⁷⁷ 元Lu-DOTATATE 以大约 7.4 GBq/周期的静脉内给药，最多 4 个周期，间隔 8 周，而卡培他滨以 1,250 mg/m²/d 口服给药 ¹⁷⁷Lu-DOTATATE 的每个周期的第 0 天到第 14 天。主要终点是客观缓解率。次要终点包括疾病控制率、无进展生存期、总生存期和不良事件。结果：纳入了 72 例患者 （中位年龄 53 岁;范围 18-79 岁）。实验组的客观缓解率为 33.3% （95% CI， 18.6-50.9%），而对照组为 30.6% （95% CI， 16.4-48.1%） （P = 0.800）。实验组和对照组的疾病控制率分别为 88.9% （95% CI， 73.9-96.9%） 和 91.7% （95% CI， 77.5-98.2%） （P = 1.000）。 实验组估计的中位无进展生存期为 29 个月 （95% CI，22-29 个月），而对照组为 31 个月 （95% CI，29-32 个月） （P = 0.401）。两组均未达到中位总生存期 （P = 0.876）。总体而言，实验组有 7 名患者发生至少 3 级不良事件，而对照组有 6 名患者 （P = 0.759）。结论：根据该试验的结果，在晚期 1/2 级 GEP-NETs 中，在 ¹⁷⁷Lu-DOTATATE 中加入低剂量卡培他滨并未导致卓越的影像学反应。需要进一步的研究来评估其在高级别 NET 中的潜在作用。