Multicenter phase 2 trial of Lu-177 dotatate versus sunitinib for metastatic progressive neuroendocrine tumors of the pancreas

The randomized, non-comparative phase 2 OCLURANDOM trial, at ten centers in France evaluated the antitumor activity and safety of [¹⁷⁷Lu]Lu-dotatate in patients with metastatic pancreatic neuroendocrine tumors (PanNETs). Patients aged 18 years or older with pretreated, progressive, somatostatin receptor-positive metastatic PanNETs and and ECOG performance status of 0-2 were randomly assigned (1:1) to receive intravenous [¹⁷⁷Lu]Lu-dotatate (7.4 GBq every 8 weeks up to four cycles) with concomitant amino acid infusion (n=41) or oral sunitinib (37.5 mg once daily; n=43). The primary endpoint was progression-free survival (PFS) at 12 months. Median follow-up was 72.5 months (IQR 61.4-88.4). PFS rate at 12 months was 80.5% (90% CI 67.5-89.9) in the [¹⁷⁷Lu]Lu-dotatate group versus 41.9% (29.1-55.5) in the sunitinib group. Grade 3-4 adverse events occurred in 44% of patients in the [¹⁷⁷Lu]Lu-dotatate group and 72% of patients in the sunitinib group. There was a 10.3 point difference in the Global Health Status score between the two groups in favor of [¹⁷⁷Lu]Lu-dotatate. Grade 2 or worse late adverse events were reported in 60% of patients in the [¹⁷⁷Lu]Lu-dotatate group and 43% of patients in the sunitinib group. One treatment-related death (acute leukemia) occurred in the [¹⁷⁷Lu]Lu-dotatate group. The authors conclude that these results show significant antitumor efficacy and tolerability of [¹⁷⁷Lu]Lu-dotatate in patients with pretreated, progressive, somatostatin receptor-positive PanNETs. Late adverse events were reported in the [¹⁷⁷Lu]Lu-dotatate group that might affect the tolerance of subsequent lines of treatment.