神経内分泌腫瘍患者における177Lu-ドタテート/カペシタビン併用療法と177Lu-ドタテート単剤療法を比較する多施設共同第II相ランダム化比較試験

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-[DOTA0,Tyr3]octreotate (177Lu-Dotatate) is an effective and safe treatment for patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET). While 177Lu-Dotatate prolongs progression-free survival (PFS) and preserves quality of life (QoL), objective response rates (ORR) remain limited. Capecitabine, as radiosensitizer, could increase efficacy without increasing 177Lu-Dotatate activity. This phase II randomized controlled trial investigated the additional cytotoxic or radiosensitizing effect of capecitabine in combination with 177Lu-Dotatate.

Patients with advanced somatostatin receptor positive GEP NET or bronchopulmonary NET were scheduled for four cycles of 7.4 GBq 177Lu-Dotatate and capecitabine or 177Lu-Dotatate alone. Capecitabine (1650 mg/m2/day) was administered for two weeks from the start of each PRRT cycle. Primary endpoints were ORR, PFS and median overall survival (OS). Secondary endpoints included biochemical response, adverse events and QoL.

111 of the 200 predefined patients were randomized for 177Lu-Dotatate/capecitabine (n=50) or 177Lu-Dotatate (n=61). According to the intention-to-treat analysis, ORR was 32% for 177Lu-Dotatate/capecitabine group versus 46% for 177Lu-Dotatate group (p=0.348). Treatment with 177Lu-Dotatate/capecitabine did not prolong median PFS (45.7 versus 31.7 months, p=0.629) or median OS (75.8 versus 61.4 months, p=0.530). Quality-adjusted life years (QALYs) were lower in the 177Lu-Dotatate/capecitabine group (1.30±0.48 versus 1.47±0.48, p=0.014).

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