A Multicenter Phase II Randomized Controlled Trial Comparing 177Lu-Dotatate/Capecitabine Combination Treatment with 177Lu-Dotatate Monotherapy in Patients with Neuroendocrine Tumors.

Whereas 177Lu-Dotatate prolongs progression-free survival(PFS) and preserves quality of life (QoL), objective response rates (ORR) remain limited.

尽管177Lu-Dotatate延长了无进展生存期（PFS）并保持了生活质量（QoL），但客观缓解率（ORR）仍然有限。

Capecitabine, as a radiosensitizer, could increase efficacy without increasing 177Lu-Dotatate activity.

作为放射增敏剂的卡培他滨，可以在不增加177Lu-Dotatate活性的情况下提高疗效。

This phase II randomized controlled trialinvestigated the additional cytotoxic or radiosensitizing effect of capecitabine in combination with 177Lu-Dotatate.

这项II期随机对照试验研究了卡培他滨与177Lu-Dotatate联合使用时的额外细胞毒性或放射增敏效果。

patients_and_methods

Patients with advanced somatostatin receptor-positive GEP NET or bronchopulmonary NET were scheduled to receive four cycles of 7.4 GBq 177Lu-Dotatate and capecitabine or 177Lu-Dotatate alone.

计划为晚期胃肠道胰腺神经内分泌肿瘤或支气管肺神经内分泌肿瘤患者进行四周期的7.4 GBq 177Lu-Dotatate联合卡培他滨或单独使用177Lu-Dotatate治疗。

Capecitabine (1,650 mg/m2/day) was administered for 2 weeks from the start of each PRRT cycle.

从每次肽受体放射性核素治疗（PRRT）周期开始时，连续两周给予卡培他滨（每日1,650 mg/m2）。

Primary endpoints were ORR, PFS, and median overall survival(OS).

主要终点包括客观缓解率（ORR）、无进展生存期（PFS）和中位总生存期（OS）。

Secondary endpoints included biochemical response, adverse events, and QoL.

次要终点包括生化反应、不良事件和生活质量（QoL）。

Results

A total of 111 of the 200 predefined patients were randomized for 177Lu-Dotatate/capecitabine (n = 50) or 177Lu-Dotatate (n = 61).

在200名预先定义的患者中，共有111名患者被随机分配接受177Lu-Dotatate/卡培他滨（n=50）或177Lu-Dotatate（n=61）。

According to the intention-to-treatanalysis, the ORR was 32% for the 177Lu-Dotatate/capecitabine group versus 46% for the 177Lu-Dotatate group (P = 0.348).

根据意向治疗分析，177Lu-Dotatate/卡培他滨组的客观缓解率（ORR）为32%，而177Lu-Dotatate组为46%（P = 0.348）。

Treatment with 177Lu-Dotatate/capecitabine did not prolong median PFS (45.7 vs. 31.7 months, P = 0.629) or median OS (75.8 vs. 61.4 months, P = 0.530).

使用177Lu-Dotatate/卡培他滨治疗并未延长中位无进展生存期（45.7个月对比31.7个月，P = 0.629）或中位总生存期（75.8个月对比61.4个月，P = 0.530）。

Quality-adjusted life years (QALY) were lower in the 177Lu-Dotatate/capecitabine group (1.30 ± 0.48 vs. 1.47 ± 0.48, P = 0.014).

177Lu-Dotatate/卡培他滨组的生活质量调整年（QALY）较低（1.30 ± 0.48对比1.47 ± 0.48，P = 0.014）。

Conclusions

In this prematurely closed phase II study, 177Lu-Dotatate/capecitabine did not improve ORR or prolong PFS and OS in patients with advanced NET compared with 177Lu-Dotatate alone and was associated with reduced QALY.

在这项提前终止的II期研究中，177Lu-Dotatate/卡培他滨并未改善晚期神经内分泌肿瘤患者的客观缓解率或无进展生存期和总生存期，与单独使用177Lu-Dotatate相比，并且与降低的生活质量调整年相关。