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

Clinical Snapshot

Key Findings

• P Value: ORR p=0.348, PFS p=0.629, OS p=0.530

• Effect Size: No significant benefit for combination therapy across primary endpoints

• Primary Outcome: Objective response rate: 32% (combination) vs 46% (monotherapy), p=0.348

• Nnt Or Sensitivity: Not applicable - no significant treatment benefit demonstrated

• Confidence Interval: Not reported in abstract

Clinical Application

177Lu-Dotatate monotherapy remains standard; combination adds complexity without benefit Relevant to Australian practice where 177Lu-Dotatate is PBS-listed for NET. Results support current monotherapy approach rather than combination Patients with advanced somatostatin receptor-positive neuroendocrine tumors eligible for PRRT

Abstract

PURPOSE: 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). Whereas 177Lu-Dotatate prolongs progression-free survival (PFS) and preserves quality of life (QoL), objective response rates (ORR) remain limited. Capecitabine, as a 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 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. Capecitabine (1,650 mg/m2/day) was administered for 2 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. RESULTS: A total of 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, the ORR was 32% for the 177Lu-Dotatate/capecitabine group versus 46% for the 177Lu-Dotatate group (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). 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). 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.

References

1. 1.Becx, M. N., Hofland, J., Krenning, E. P., Wyld, D. K., Nonnekens, J., Verburg, F. A., Brabander, T., van Busschbach, J. J. V., & de Herder, W. W. (2026). A Multicenter Phase II Randomized Controlled Trial Comparing 177Lu-Dotatate/Capecitabine Combination Treatment with 177Lu-Dotatate Monotherapy in Patients with Neuroendocrine Tumors. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-1884