Satapathy Swayamjeet, Aggarwal Piyush, Sood Ashwani, Chandekar Kunal R, Das Chandan K, Gupta Rajesh, Khosla Divya, Das Namrata, Kapoor Rakesh, Kumar Rajender, Singh Harmandeep, Shukla Jaya, Kumar Ajay, Mittal Bhagwant Rai
Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India;
J Nucl Med. 2025 Feb 3;66(2):238-244. doi: 10.2967/jnumed.124.268617.
Lu-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 Lu-DOTATATE with radiosensitizing low-dose capecitabine to be effective in advanced NETs. However, this has not been validated in prospective randomized-controlled trials. 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 Ga-DOTANOC PET/CT, were randomly assigned in a 1:1 ratio to Lu-DOTATATE plus capecitabine (experimental arm) or Lu-DOTATATE only (control arm). Lu-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/m/d orally from day 0 to day 14 of each cycle of Lu-DOTATATE. The primary endpoint was the objective response rate. Secondary endpoints included the disease control rate, progression-free survival, overall survival, and adverse events. 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 ( = 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 ( = 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 ( = 0.401). The median overall survival was not reached in either arm ( = 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 ( = 0.759). Based on the results of this trial, the addition of low-dose capecitabine to Lu-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.
镥-奥曲肽已成为晚期高分化1/2级胃肠胰神经内分泌肿瘤（GEP-NETs）的一种可行治疗策略。少数回顾性研究表明，镥-奥曲肽与放射增敏低剂量卡培他滨联合使用对晚期神经内分泌肿瘤有效。然而，这尚未在前瞻性随机对照试验中得到验证。在这项由研究者发起的、平行组、开放标签的2期试验中，1/2级GEP-NETs患者，在镓-奥曲肽PET/CT上有进展性生长抑素受体阳性、局部晚期或转移性疾病，按1:1比例随机分配至镥-奥曲肽加卡培他滨组（试验组）或仅镥-奥曲肽组（对照组）。镥-奥曲肽以约7.4GBq/周期静脉给药，最多4个周期间隔8周，而卡培他滨在镥-奥曲肽每个周期的第0天至第14天以1250mg/m²/天口服。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。72例患者（中位年龄53岁；范围18 - 79岁）入组。试验组客观缓解率为33.3%（95%CI，18.6 - 50.9%），对照组为30.6%（95%CI，16.4 - 48.1%）（P = 0.800）。试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）。试验组估计的中位无进展生存期为29个月（95%CI，22 - 29个月），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，试验组7例患者出现至少3级不良事件，对照组6例患者出现（P = 0.759）。基于该试验结果，在晚期1/2级GEP-NETs中，在镥-奥曲肽基础上加用低剂量卡培他滨并未带来更好的影像学缓解。需要进一步研究评估其在高级别神经内分泌肿瘤中的潜在作用。
